Biology subjects

Liao, X.-H.

Publications and source records attributed to Liao, X.-H..

4 recordsLinked to original sources

bioRxiv2021

AAV9-MCT8 delivery at juvenile stage ameliorates neurological and behavioral deficits in an AHDS mouse model

Allan-Herndon-Dudley syndrome (AHDS) is a severe X-linked intellectual and psychomotor disability disorder accompanied by abnormal thyroid hormone (TH) levels. AHDS is caused by inactivating mutations in the monocarboxylate transporter 8 (MCT8), a specific TH transporter widely expressed in the central nervous system. MCT8 gene mutations cause impaired transport of TH across brain barriers, leading to insufficient neural TH supply. There is currently no successful therapy for the neurological symptoms. AAV9-based gene therapy is a promising approach to treat monogenic neurological disorders. Here, the potential of this approach was tested in the well-established double knockout (dKO) Mct8-/y;Oatp1c1-/- mouse model of AHDS, which displays disease-relevant neurological and TH phenotypes. Systemic intravenous delivery of AAV9-MCT8 at a juvenile stage led to improved locomotor and cognitive function, as well as rescue of T3-brain content and T3-related gene expression. This preclinical study indicates that this gene therapy may improve the neurological symptoms of AHDS patients.

neuroscience↗

bioRxiv2020

STAT3 inhibits Myocardin induced cardiac hypertrophy

BackgroundIn order to explore the molecular mechanism of cardiomyocyte-dependent myocardial gene expression and cardiomyocyte differentiation in cardiac hypertrophy, and to provide new insights for cardiac hypertrophy. MethodsCardiac myocytes were isolated from day 1-3 Sprague-Dawley rat pups. Real time quantitative PCR, western blot and immunocytochemistry Assay were used to detect the expression and localization of related genes. CO-IP was used to detect direct protein interactions between Myocardin and STAT3. Luciferase reporter assay and chromatin immunoprecipitation were used to detect the binding of Myocardin to the promoter of a downstream target gene. Microinjection of zebrafish embryos was used to examine the effects of STAT3 and Myocardin interactions on cardiac development in vivo ResultsThe N-terminus of STAT3 directly binds to the basic domain of myocardin and inhibits the transcriptional activity of Myocardin-mediated cardiac-specific genes ANF and -actinin, thereby inhibiting their expression, and further inhibit myocardin-mediated cardiac hypertrophy in vivo. ConclusionsIn summary, our report states that signal transduction and transcriptional activation factor 3 (STAT3) are inhibitors of the major cardiac hypertrophic transcription factor Myocardiin, which is required for cardiomyocyte differentiation. The STAT3-cardiacin interaction identified nuclear hormone receptor-mediated and cardiac-specific gene-regulated convergence sites and suggested a possible mechanism for cardioprotective effects.

cell biology↗

bioRxiv2020

MiR-17-5p regulates proliferation and apoptosis of uterine fibroids via targeting ESR1

The treatment of uterine fibroids and the development of new drugs depend on adeeper understanding of the developmental mechanisms of uterine fibroids. Here, the role of ESR1 and miR-17 on the uterine fibroids cell proliferation and apoptosis and their relationship were investigated in USMCs. Our results showed that ESR1 increased the proliferation of USMCs and inhibited their apoptosis. In addition, ESR1 could directly bind the promoter regionof TP53 and inhibit its expression. MiR-17 increased the apoptosis of USMCs and inhibited their proliferation via decreasing the level of ESR1 by targeting its 3UTR. Our research provides a new understanding of the development of uterine fibroids and provides a theoretical basis for the treatment of uterine fibroids.

molecular biology↗

bioRxiv2019

Vps34/PIK3C3 deletion in thyroid impairs thyroid hormonogenesis and autophagic flux

BACKGROUNDThe production of thyroid hormones (T3, T4) depends on thyroid organization in follicles, lined by a monolayer of thyrocytes with strict apico-basal polarity. Polarization supports vectorial transport of thyroglobulin for storage into, and recapture from, the colloid. It also allows selective addressing of channels, transporters, pumps and enzymes to their appropriate basolateral (NIS and Na+/K+-ATPase) or apical membrane domain (pendrin, anoctamin, DUOX2, DUOXA2 and TPO). How these actors of T3/T4 synthesis reach their final destination remains poorly understood. Vps34/PIK3C3 is now recognized as a main component in the general control of vesicular trafficking and of cell homeostasis via autophagy. We recently reported that conditional Vps34 inactivation in kidney proximal tubular cells by Pax8-driven excision prevents normal addressing of apical membrane proteins and causes abortive macroautophagy. METHODSVps34 was inactivated using a Pax8-driven Cre recombinase system. The impact of Vps34 inactivation in thyrocytes was analyzed by histological, immunolocalization and mRNA expression profiling. Thyroid hormone synthesis was assayed by 125I injection and by serum plasma analysis. RESULTSVps34cKO mice were born at the expected Mendelian ratio and showed normal growth until postnatal day 14, then stopped growing and died at around 1 month of age. We therefore analyzed thyroid Vps34cKO before postnatal day 14. We found that loss of Vps34 in thyrocytes causes: (i) disorganization of thyroid parenchyma with abnormal thyrocyte and follicular shape and reduced PAS+ colloidal spaces; (ii) impaired 125I organification at comparable uptake and frequent occurrence of follicles with luminal thyroglobulin but non-detectable T4-bearing thyroglobulin; (iii) severe non-compensated hypothyroidism with extremely low T4 levels (<0.25 {+/-} 1.5 g/dL) and huge TSH plasma levels (19,300 {+/-} 10,500 mU/L); (iv) intense signal in thyrocytes for the lysosomal membrane marker, LAMP-1, as well as thyroglobulin and the autophagy marker, p62, indicating defective proteolysis. CONCLUSIONSWe conclude that Vps34 is crucial for thyroid hormonogenesis, at least by controlling delivery of apical actors responsible for biogenesis of thyroid hormones on Tg as well as defective proteolytic T3/T4 excision in lysosomes.

cell biology↗