Toshniwal, Priyanka and Nguyen, Michelle and Guédin, Aurore and Viola, Helena and Ho, Diwei and Kim, Yongeun and Bhatt, Uditi and Bond, Charles S. and Hool, Livia and Hurley, Laurence H. and Mergny, Jean‐Louis and Fear, Mark and Wood, Fiona and Swaminathan Iyer, Killugudi and Smith, Nicole M. (2019) TGF‐β‐induced fibrotic stress increases G‐quadruplex formation in human fibroblasts. FEBS Letters. ISSN 0014-5793
Full text not available from this repository.Abstract
Scar formation after wound healing is a major medical problem. A better understanding of the dynamic nuclear architecture of the genome during wound healing could provide insights into the underlying pathophysiology and enable novel therapeutic strategies. Here, we demonstrate that TGF-β-induced fibrotic stress increases formation of the dynamic secondary DNA structures called G-quadruplexes in skin fibroblasts, which is coincident with increased expression of collagen 1. This G-quadruplex formation is attenuated by a small molecule inhibitor of intracellular Ca2+ influx and an anti-fibrotic compound. In addition, we identify G-quadruplex-forming sequences in the promoter region of COL1A1, which encodes collagen 1, and confirm their ability to form G-quadruplex structures under physiologically relevant conditions. Our findings reveal a link between G-quadruplexes and scar formation that may lead to novel therapeutic interventions.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 19 Nov 2019 22:44 |
| Last Modified: | 19 Nov 2019 22:44 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/870 |
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