Biology subjects

Yang, M.

Publications and source records attributed to Yang, M..

At least 307 records · Page 17Linked to original sources

bioRxiv2021

Genomic insights into the differentiated population admixture structure and demographic history of North East Asians

North China and South Siberia, mainly populated by Altaic-speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroad for the initial peopling of America and western-eastern trans-continental communication. Yet, the complex scenarios of genetic origin, population structure, and admixture history of North-East Asia remain to be fully characterized, especially for Mongolic people in China with a genome-wide perspective. Thus, we genotyped genome-wide SNPs for 510 individuals from 38 Chinese Mongolic, Tungusic, and Sinitic populations to explore the sharing alleles and haplotypes within the studied groups and following merged it with 3508 modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified significant substructures within Altaic-speaking populations with the primary common ancestry linked to the Neolithic northern East Asians: Western Turkic people harbored more western Eurasian ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed dominant Neolithic Mongolian Plateau (MP) or ARB ancestry; Southern Mongolic people in China owned obvious genetic impact from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians and the latter retained the dominant YRB and ARB Neolithic ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountain possessed a strong genetic affinity with Neolithic MP people, supporting the hypothesis of their eastern Eurasian origin and long-distance migration history. We also illuminated that historic pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to southern ones. We finally found natural signatures in Mongolians associated with alcohol metabolism. Generally, our results not only illuminated that complex population migration and admixture of Neolithic ancestral sources from the MP or ARB played an important role in the spread of Altaic-speaking populations and Proto-Altaic language, which partly supported the Northeast Asia-origin hypothesis, but also demonstrated that the observed multi-sources of genetic diversity contributed significantly to the modern existing extensive ethnolinguistic diversity in North-East Asia.

genomics↗

bioRxiv2021

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution genome-wide InDels and SNPs

Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpa people by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 3324 individuals in 382 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this updated InDel panel is informative and polymorphic in Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in the highland East Asians. Descriptive findings from the PCA, ADMIXTURE and TreeMix-based phylogeny suggested that Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Sherpa people had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpa, core Tibetans and Chokhopani formed one clade which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from FineStructure and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL, and iHH12 showed signatures associated with disease susceptibility in Sherpa people. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the low-density forensic markers and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.

genetics↗

bioRxiv2021

Wuschel2 enables highly efficient CRISPR/Cas-targeted genome editing during rapid de novo shoot regeneration in sorghum

For many important crops, including sorghum, the use of CRISPR/Cas technology is limited not only by the delivery of the gene-modification components into a plant cell, but more critically, by the ability to regenerate a fertile plant from the engineered cell through conventional tissue culture methods. Here, we report that Wuschel2 (Wus2)-enabled sorghum (Sorghum bicolor L.) transformation increases not only the efficiency of transgenic plant recovery, but also increases the observed efficiency of CRISPR/Cas-targeted genome editing within the population of T0 plants. Using Agrobacterium-mediated transformation, we have demonstrated Wus2-induced direct somatic embryo formation and regeneration, bypassing genotype-dependent callus formation and significantly shortening the tissue culture cycle time. This method also increased regeneration capacity, resulting in higher transformation efficiency across different sorghum genotypes. Subsequently, advanced excision systems and "altruistic" transformation technology have been developed to generate high-quality morphogenic gene-free and/or selectable marker-free sorghum events. Finally, we demonstrated up to an additional 6.8-fold increase in CRISPR/Cas9-mediated gene dropout frequency using Wus2-enabled, Agrobacterium-mediated transformation (compared to the control treatment with no Wus2), across various targeted loci in different sorghum genotypes. Wus2-enabled genome editing may be applicable to other crops and increasingly popular in planta transformation strategies.

developmental biology↗

bioRxiv2021

CCPE: Cell Cycle Pseudotime Estimation for Single Cell RNA-seq Data

The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies makes it possible to characterize cellular heterogeneity by detecting and quantifying transcriptional changes at the single-cell level. Pseudotime analysis enables to characterize the continuous progression of various biological processes, such as cell cycle. Cell cycle plays an important regulatory role in cell fate decisions and differentiation and is also often regarded as a confounder in scRNA-seq data analysis when analyzing the role of other factors on transcriptional regulation. Therefore, accurate prediction of cell cycle pseudotime and identify cell stages are important steps for characterizing the development-related biological processes, identifying important regulatory molecules and promoting the analysis of transcriptional heterogeneity. Here, we develop CCPE, a novel cell cycle pseudotime estimation method to characterize cell cycle timing and determine cell cycle phases from single-cell RNA-seq data. CCPE uses a discriminative helix to characterize the circular process and estimates pseudotime in the cell cycle. We evaluated the model performance based on a variety of simulated and real scRNA-seq datasets. Our results indicate that CCPE is an effective method for cell cycle estimation and competitive in various downstream analyses compared with other existing methods. CCPE successfully identified cell cycle marker genes and is robust to dropout events in scRNA-seq data. CCPE also has excellent performance on small datasets with fewer genes or cells. Accurate prediction of the cell cycle in CCPE effectively contributes to cell cycle effect removal across cell types or conditions.

bioinformatics↗

bioRxiv2021

Deep Learning Approach to Genomic Breakage Study from Primary Sequence

Identifying the molecular mechanisms related to genomic breakage is an important goal of cancer mechanism studies. Among the diverse location of the breakpoints of structural variants, the fusion genes, which have the breakpoints in the gene bodies and typically identified from RNA-seq data, can provide a highlighted structural variant resource for studying the genomic breakages with expression and potential pathogenic impacts. In this study, we developed FusionAI which utilizes deep learning to predict gene fusion breakpoints based on primary sequences and let us identify fusion breakage code and genomic context. FusionAI leverages the known fusion breakpoints to provide a prediction model of the fusion genes from the primary genomic sequences via deep learning, thereby helping researchers a more accurate selection of fusion genes and better understand genomic breakage. HighlightsO_LIFusionAI, a 9-layer deep neural network, predicts fusion gene breakpoints from a DNA sequence C_LIO_LIFusonAI reduce the cost and effort for validating fusion genes by decreasing specificity C_LIO_LIHigh feature importance scored regions were apart 100nt on average from the exon junction breakpoints C_LIO_LIHigh feature importance scored regions overlapped with 44 different human genomic features C_LIO_LITranscription factor fusion genes are targeted by the GC-rich motif TFs C_LIO_LIFusionAI gives less scores to the non-disease derived breakpoints C_LI

bioinformatics↗

bioRxiv2021

The First High-Quality Reference Genome of Sika Deer Provides Insights for High-Tannin Adaptation

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement in the elucidation of the genomics of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of UGT genes in a subfamily. The first chromosome-level assembly and genetic characterization of the tolerance toa highly toxic diet suggest that the sika deer genome will serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

genomics↗

bioRxiv2021

Design and immunogenicity of a Pan-SARS-CoV-2 synthetic DNA vaccine

Here we have employed SynCon(R) design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants of concern (VOC). Compared to WT and VOC-matched vaccines which showed reduced cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster challenge model demonstrated that INO-4802 conferred superior protection following intranasal B.1.351 challenge. Protection against weight loss associated with WT, B.1.1.7, P.1 and B.1.617.2 challenge was also demonstrated. Vaccinated hamsters showed enhanced humoral responses against VOC in a heterologous WT vaccine prime and INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOC as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.

immunology↗

bioRxiv2021

Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta

The majority of clinical deaths among patients with triple-negative breast cancer (TNBC) are caused by uncontrolled cell proliferation and aggressive metastases, which is regulated by hyperactive glycogen synthase kinase 3 beta (GSK3{beta}); however, the underlying mechanisms remain largely unknown. In the present study, we found that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) was specifically upregulated in TNBC, compared with that in normal tissues and non-TNBC. High PPP1R14C expression correlated significantly with shorter 5-year relapse-free survival and overall survival in patients with TNBC. Overexpressing PPP1R14C promoted, while suppression of PPP1R14C decreased the cell proliferation and the aggressive phenotype of TNBC cells, in vitro and in vivo. Importantly, we revealed that PPP1R14C interacted with and inactivated type 1 Ser/Thr protein phosphatase (PP1) to sustain GSK3{beta} phosphorylation at S9, and induced the ubiquitylation and degradation of non-phosphorylated GSK3{beta} (S9A) via recruiting E3 ligase, TRIM25. Furthermore, treating with C2 ceramide (C2), which recovered kinase activity of GSK3{beta}, resulted in tumor growth inhibition in PPP1R14C-overexpressing TNBC cells. Our findings reveal a novel mechanism whereby PPP1R14C sustains inactive GSK3{beta}, which might lead to targeted therapy for TNBC.

cancer biology↗

bioRxiv2021

Deep oncopanel sequencing reveals fixation time- and within block position-dependent quality degradation in FFPE processed samples

Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized normal cell line was used to create FFPE samples with four different pre-tissue processing formalin fixation times. A total of 96 FFPE sections were then distributed to different laboratories for targeted sequencing analysis by four oncopanels, and variants resulting from technical error were identified. Tissue sections that failed more frequently showed low cellularity, lower than recommended library preparation DNA input, or target sequencing depth. Importantly, sections from block surfaces were more likely to show FFPE-specific errors, akin to "edge effects" seen in histology, and the depth of formalin damage was related to fixation time. To assure reliable results, we recommend avoiding the block surface portion and restricting mutation detection to genomic regions of high confidence.

cancer biology↗

bioRxiv2021

Optimizing touchscreen measures of rodent cognition by eliminating image bias

For the last twenty years, the Bussey-Saksida touchscreen-based operant conditioning platform has evolved in close parallel alongside the Cambridge Neuropsychological Test Automated Battery (CANTAB) to produce batteries of tests for studying complex cognitive functions in rodents that are increasingly analogous to human diagnostic tests and greatly narrow the translational gap in cognition research. Naturally, with this increasing usefulness comes increasing use, particularly by non-experts. This necessitates a greater understanding of, and a better controlling for, confounding factors that may limit the systems ability to optimally detect cognitive deficits when used as a widely accessible and commercially available standardized task. In the present study, we show a strong image preference bias in a standard pairwise discrimination task with a widely used spider-plane image pairing in a putative animal model for intellectual disability. This bias greatly influenced the performance of our experimental mice, significantly affecting the length of time it took mice to complete the task, their progress over time, and several accessory measures usefully recorded by the Bussey-Saksida touchscreen system. We further show that this bias can be corrected by using more similar image pairings without sacrificing the animals ability to learn to distinguish the stimuli. This approach eliminated all significant stimuli specific differences seen with the spider-plane pairing. We then analyzed the pixel composition of the various stimuli to suggest that the bias is due to a difference in image brightness. These findings highlight the importance of carefully modulating paired touchscreen stimuli to ensure equivalence prior to learning and the need for more studies of visual perception in mice, particularly as it relates to their performance in cognitive assays.

animal behavior and cognition↗

bioRxiv2021

Functional, metabolic and transcriptional maturation of stem cell derived beta cells

Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in stem cell-derived islet (SC-islet) generation, detailed characterization of their functional properties has not been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and comprehensively benchmarked them against primary adult islets. Biphasic glucose stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and increased alpha cells. Electrophysiology and exocytosis of SC-islets were comparable to adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of murine engraftment revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.

developmental biology↗

bioRxiv2021

A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.

immunology↗

bioRxiv2021

Comprehensive evaluation of ACE2 expression in female ovary by single-cell RNA-seq analysis

Pneumonia induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) via ACE2 receptor may affect many organ systems like lung, heart and kidney. An autopsy report revealed positive SARS-Cov-2 detection results in ovary, however, the developmental-stage-specific and cell-type-specific risk in fetal primordial germ cells (PGCs) and adult women ovary remained unclear. In this study, we used single-cell RNA-sequencing (scRNA-seq) datasets spanning several developmental stages of ovary including PGCs and cumulus-oocyte complex (COC) to investigate the potential risk of SARS-CoV-2 infection. We found that PGCs and COC exhibited high ACE2 expression. More importantly, the ratio of ACE2-positive cells was sharply up-regulated in primary stage and ACE2 was expressed in all oocytes and cumulus cells in preovulatory stage, suggesting the possible risk of SARS-CoV-2 infection in follicular development. CatB/L, not TMPRSS2, was identified to prime for SARS-CoV-2 entry in follicle. Our findings provided insights into the potential risk of SARS-CoV-2 infection during folliculogenesis in adulthood and the possible risk in fetal PGCs.

developmental biology↗

bioRxiv2021

Engineering the Immune Adaptor Protein STING as a Biologic

Activation of the stimulator of interferon genes (STING) pathway through cyclic dinucleotides (CDNs) has been explored extensively as potent vaccine adjuvants against infectious diseases as well as to increase tumor immunogenicity towards cancer immunotherapy in solid tumors. Over the last decade, a myriad of synthetic vehicles, including liposomes, polymers, and other nanoparticle platforms, have been developed to improve the bioavailability and therapeutic efficacy of STING agonists in preclinical mouse models. In comparison to synthetic materials, protein-based carriers represent an attractive delivery platform owing to their biocompatibility, amenability to genetic engineering, and intrinsic capacity to form well-defined structures. In the present work, we have engineered the immune adaptor STING as a protein-based delivery system for efficient encapsulation and intracellular delivery of CDNs. Through genetic fusion with a protein transduction domain, the recombinant STING can spontaneously penetrate cells to markedly enhance the delivery of CDNs in a mouse vaccination model and a syngeneic mouse melanoma model. Moreover, motivated by recent findings that certain tumor cells can evade immune surveillance via loss of STING expression, we further unveiled that our STING platform can serve as a functional vehicle to restore the STING signaling in a panel of lung and melanoma cell lines with impaired STING expression. Taken together, our STING-based protein delivery platform may offer a unique direction towards targeting STING-silenced tumors as well as augmenting the efficacy of STING-based vaccine adjuvants.

bioengineering↗

bioRxiv2021

Genomic analyses of 10,376 individuals provides comprehensive map of genetic variations, structure and reference haplotypes for Chinese population

Here, we initiated the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing individuals and 5,481 high-density genotyping individuals. We identified 80.99 million SNPs and INDELs, of which 38.6% are novel. The genetic evidence of Chinese population structure supported the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains. The genetic architecture within North Han was more homogeneous than South Han, and the history of effective population size of Lingnan began to deviate from the other three regions from 6 thousand years ago. In addition, we identified a novel locus (SNX29) under selection pressure and confirmed several loci associated with alcohol metabolism and histocompatibility systems. We observed significant selection of genes on epidermal cell differentiation and skin development only in southern Chinese. Finally, we provided an online imputation server (https://wbbc.westlake.edu.cn/) which could result in higher imputation accuracy compared to the existing panels, especially for lower frequency variants.

genetics↗

bioRxiv2021

MMP12 Knockout Prevent Weight and Muscle Loss Induced by Cancer Cachexia

Weight loss and muscle wasting can have devastating impacts on survival and quality of life of patients with cancer cachexia. Here, we have established a hybrid mouse of ApcMin/+ mice and MMP12 knockout mice (ApcMin/+; MMP12-/-) and found that knockout MMP12 can suppress the weight and muscle loss of ApcMin/+ mice. In detail, we found that interleukin 6 was highly upregulated in the serum of cancer patients and MMP12 was increased in muscle of tumor-bearing mice. Interestingly, the interleukin 6 secreted by tumor cells led to MMP12 overexpression in the macrophages, which further resulted in degradation of insulin and insulin-like growth factor 1 and interruption of glycolipid metabolism. Notably, depletion of MMP12 prevented weight loss of ApcMin/+ mice. Our study uncovers the critical role of MMP12 in controlling weight and highlights the great potential of MMP12 in the treatment of cancer cachexia.

cancer biology↗

bioRxiv2021

Astrocyte-derived ApoE is Required for the Maturation of Injury-induced Hippocampal Neurons and Regulates Cognitive Recovery After Traumatic Brain Injury

Polymorphisms in the apolipoprotein E (ApoE) gene confer a major genetic risk for the development of late-onset Alzheimers disease (AD) and are predictive of outcome following traumatic brain injury (TBI). Alterations in adult hippocampal neurogenesis have long been associated with both the development of AD and recovery following TBI, and ApoE is known to play a role in this process. In order to determine how ApoE might influence hippocampal injury-induced neurogenesis, we developed a novel conditional system whereby functional ApoE from astrocytes was ablated just prior to injury. While successfully ablating 90% of astrocytic ApoE just prior to a closed cortical impact injury in mice, we observed an attenuation in the development of newly born neurons using a GFP-expressing retrovirus, but not in existing hippocampal neurons visualized with a Golgi stain. Intriguingly, animals with a "double-hit", i.e. injury and ApoE conditionally inactivated in astrocytes, demonstrated the most pronounced impairments in the hippocampal-dependent Morris water maze test, failing to exhibit spatial memory after both acquisition and reversal training trials. In comparison, conditional knockout mice without injury displayed impairments but only in the reversal phase of the test, suggesting accumulative effects of astrocytic ApoE deficiency and traumatic brain injury on AD-like phenotypes. Together, these findings demonstrate that astrocytic ApoE is required for functional injury-induced neurogenesis following traumatic brain injury. Significance StatementApoE has long been implicated in the development of Alzheimers disease and recovery from traumatic brain injury via unknown mechanisms. Using a novel conditional ablation model of mouse ApoE and subsequent tracing of individual hippocampal neurons, we demonstrate its requirement in injury-induced neurogenesis for proper dendritic arborization and cognitive function in hippocampal-dependent learning and memory tasks.

neuroscience↗

bioRxiv2021

DsbA-L protects against diabetic renal injury through the adipo-renal axis

Disulfide-bond A oxidoreductase-like protein (DsbA-L) is an adiponectin-interacting protein that is highly expressed in adipose tissue. The adipo-renal axis involves adipocyte release of signaling molecules that are recruited to kidney and regulate kidney function. We have found that the DsbA-L modulated the progression of diabetic nephropathy, but the precise mechanism of this modulation is unknown. Here, the transgenic mice overexpressing DsbA-L protein in fat (fDsbA-L) were used to verify that the renoprotective role of DsbA-L whether by adipo-renal axis. Mice were divided into four groups: a normal (Control) group, STZ induced diabetic mice, fDsbA-L mice and diabetic fDsbA-L mice (n=6). Diabetes was induced in mice by STZ 100mg/kg and continued HFD feeding for 12 weeks. Compared with the control group, the weight, blood glucose,and urine protein levels and the pathological changes in the kidney tissue of diabetic mice were increased significantly, accompanied by increased NLRP3,caspase-1, IL-1{beta}, IL-18, FN, and Collagen1 mRNA and protein expression, which were reduced in diabetic fDsbA-L mice. Interestingly, the level of adiponectin in serum and kidney expression in diabetic mice was reduced significantly compared to that in the control group. However this change was reversed in diabetic fDsbA-L mice. These data suggest that the overexpression of DsbA-L in the adipocytes of mice can protect against diabetic renal injury through anti-inflammatory mediators,and may be mediated by the adipo-renal axis.

genetics↗