Homocysteine Induces Collagen I Expression by Downregulating Histone Methyltransferase G9a.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26192994.
- Also identified by DOI 10.1371/journal.pone.0130421 and PMC identifier 4508059.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Hyperhomocysteinemia (HHcy) leads to several clinical manifestations including hepatic fibrosis. Excess deposition of extracellular matrix (ECM) components including collagen is the eponymous lesion of liver fibrosis. In this study, we demonstrated that elevated concentration of Hcy induced the expression of collagen type I in cultured human liver cells as well as in liver tissue of HHcy mice. Meanwhile, Hcy inhibited the expression of histone methyltransferase G9a. Mechanistically, silencing endogenous G9a by siRNA enhanced the promoter activity of COL1A1 in LO2 cells. Conversely, overexpressing G9a inhibited the promoter activity of COL1A1. CHIP assay demonstrated that G9a binds to the neuron-restrictive silencer element (NRSE) on the promoter of COL1A1. Hcy treatment decreased the binding of G9a on NRSE, which in turn decreased the level of H3K9me2 on the promoter of COL1A1, led to upregulation of COL1A1. Taken together, these results provide a novel mechanism on explaining how HHcy promotes ECM production.
Medical subject headings
- Collagen Type I
- Down-Regulation
- Histocompatibility Antigens
- Histone-Lysine N-Methyltransferase
- Homocysteine