Biology subjects

Kim, E. M.

Publications and source records attributed to Kim, E. M..

4 recordsLinked to original sources

bioRxiv2024

An evolutionarily conserved role for VEGF signaling in the expansion of non-vascular tissue during regeneration.

Salamanders are capable of regenerating whole limbs throughout life, a feat that is unmatched within tetrapods. Limb regeneration is dependent upon the formation of a blastema, which contains undifferentiated cells capable of giving rise to most cells of the regenerated limb. Innervation is required for regeneration, along with many signaling pathways, including FGF, BMP and Wnt, but the role of VEGF signaling during salamander limb regeneration is not well understood. Here we show that VEGF signaling is essential for limb regeneration and that blastema cells and limb fibroblasts display impaired proliferation in the absence of VEGF signaling. By performing analogous experiments in planaria, which lack vasculature, we show a potential evolutionarily conserved role for VEGF in the expansion of blastema tissues that is separable from angiogenesis. Moreover, loss of VEGF signaling reduces induction of EMT-like processes, suggesting VEGF signaling functions upstream of the expression of EMT transcription factors, including Snai2. These findings highlight potential roles for VEGF signaling during regeneration which may extend beyond typical findings related to angiogenesis.

developmental biology↗

bioRxiv2024

Amputation Triggers Long-Range Epidermal Permeability Changes in Evolutionarily Distant Regenerative Organisms

Previous studies have reported that amputation invokes body-wide responses in regenerative organisms, but most have not examined the implications of these changes beyond the region of tissue regrowth. Specifically, long-range epidermal responses to amputation are largely uncharacterized, with research on amputation-induced epidermal responses in regenerative organisms traditionally being restricted to the wound site. Here, we investigate the effect of amputation on long-range epidermal permeability in two evolutionarily distant, regenerative organisms: axolotls and planarians. We find that amputation triggers a long-range increase in epidermal permeability in axolotls, accompanied by a long-range epidermal downregulation in MAPK signaling. Additionally, we provide functional evidence that pharmacologically inhibiting MAPK signaling in regenerating planarians increases long-range epidermal permeability. These findings advance our knowledge of body-wide changes due to amputation in regenerative organisms and warrant further study on whether epidermal permeability dysregulation in the context of amputation may lead to pathology in both regenerative and non-regenerative organisms. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/610385v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@81b022org.highwire.dtl.DTLVardef@52c2e9org.highwire.dtl.DTLVardef@17a5f93org.highwire.dtl.DTLVardef@118b8f6_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2021

Draft Genome of the Korean smelt (Hypomesus nipponensis) and its transcriptomic responses to heat stress in the liver and muscle

Pond smelt (Hypomesus nipponensis) is a cold-freshwater fish species as a winter economic resource of aquaculture in South Korea. Due to its high susceptibility to abnormal water temperature from global warming, a large number of smelt die in hot summer. Here, we present the first draft genome of H. nipponensis and transcriptomic changes in molecular mechanisms or intracellular responses under heat stress. We combined Illumina and PacBio sequencing technologies to generate the draft genome of H. nipponensis. Based on the reference genome, we conducted transcriptome analysis of liver and muscle tissues under normal (NT, 5{degrees}C) versus warm (HT, 23{degrees}C) conditions, to identify heat stress-induced genes and gene categories. We observed a total of 1,987 contigs, with N50 of 0.46 Mbp with a largest contig (3.03 Mbp) in the assembled genome. A total number of 20,644 protein coding genes were predicted, and 19,224 genes were functionally annotated: 15,955 genes for Gene Ontology (GO) terms; and 11,560 genes for KEGG Orthology (KO). We conducted the lost and gained genes analysis compared with three species that human, zebrafish and salmon. In the lost genes analysis, we detected smelt lost 4,461 (22.16%), 2,825 (10.62%), and 1,499 (3.09%) genes compare with above three species, respectively. In the gained genes analysis, we observed smelt gain 1,133 (5.49%), 1,670 (8.09%), and 229 (1.11%) genes compare with above species, respectively. From transcriptome analysis, a total of 297 and 331 differentially expressed genes (DEGs) with False discovery rate (FDR) < 0.05 were identified in the liver and muscle tissues, respectively. Gene enrichment analysis of DEGs indicates that up-regulated genes were significantly enriched for lipid biosynthetic process (GO:0008610, P < 0.001) and regulation of apoptotic process (GO:0042981, P < 0.01), and down-regulated genes by immune responses such as myeloid cell differentiation (GO:0030099, P < 0.001) in the liver under heat stress. In muscle tissue, up-regulated genes were enriched for hypoxia (GO:0001666, P < 0.05), transcription regulator activity (GO:0140110, P < 0.001) and calcium-release channel activity (GO:0015278, P < 0.01), and down-regulated genes for nicotinamide nucleotide biosynthetic process (GO:0019359, P < 0.01). The results of KEGG pathway analysis were similar to that of gene enrichment analysis. The draft genome and transcriptomic of H. nipponensis will be used as a useful genetic resource for functional and evolutionary studies. Our findings will improve understanding of the molecular mechanisms and heat responses and will be useful for predicting survival of the smelt and its closely related species under global warming.

genetics↗

bioRxiv2020

Differential TM4SF5-mediated SIRT1 modulation and signaling for chronic liver disease

Here we show the roles of transmembrane 4 L six family member 5 (TM4SF5) in the progression of nonalcoholic steatosis (or NAFL) to steatohepatitis (NASH). The overexpression of TM4SF5 caused nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and livers exhibited lipid accumulation, decreased SIRT1, increased SREBPs levels, and inactive STAT3 via SOCS1/3 upregulation. In older animals, TM4SF5 under an inflammatory environment increased SIRT1 expression and STAT3 activity with no significant change to SOCSs and SREBPs levels, leading to active STAT3-mediated fibrotic extracellular matrix (ECM) production. Liver tissues from clinical human patients with NAFL or NASH also showed such a TM4SF5-SIRT1-STAT3-ECM relationship correlated with fibrosis score and age. Ligand-independent and TM4SF5-mediated STAT3 activity led to collagen I and laminins/laminin {gamma}2 expression in hepatic stellate cells and hepatocytes, respectively. Laminin {gamma}2 suppression abolished CCl4-mediated liver damage and ECM production and reduced SIRT1 and active-STAT3, but did not alter SREBP1 or SOCSs levels. These findings suggest that TM4SF5, CCL20, SIRT1, and/or laminin {gamma}2 may be promising therapeutic targets against liver disease.

cell biology↗