α5 integrin regulates hepatic tight junctions through SRC-TET1-mediated DNA hydroxymethylation
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Updated: Aug 19, 2025

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling
Published on: December 18, 2017
Yuejiao Ma1, Weitao Zhang2, Weihong Li1
1Department of Cell Biology, Capital Medical University, Beijing 100069, China.
Abstract:
The functional tight junctions' integrity plays an important role in liver physiology. A variety of liver diseases have been associated with the perturbation of tight junctions. Herein, we showed that the lower expression of α5 integrin in hepatocytes in patients with liver cirrhosis is associated with matrix deposition in the space of Disse. Selective silencing of α5 integrin in hepatocytes compromised the ultrastructure of tight junctions by downregulating claudin 1 in an SRC (proto-oncogene, non-receptor tyrosine kinase) signaling-dependent manner. α5 integrin signaling induced SRC-TET-mediated changes in 5-hydroxymethylcytosine and 5-methylcytosine levels in hepatocytes in vitro and in vivo. hMeDIP sequencing showed intergenic hypohydroxymethylation of the claudin 1 gene in hepatocytes after α5 integrin silencing in mice. Therefore, understanding the mechanisms regulating hepatic tight junction integrity in which α5 integrin-SRC signaling and epigenetic modifications cooperate might help advance the development of useful diagnostics and therapeutic approaches for liver disease.
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