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TGF‐β‐induced fibrotic stress increases G‐quadruplex formation in human fibroblasts
Author(s) -
Toshniwal Priyanka,
Nguyen Michelle,
Guédin Aurore,
Viola Helena,
Ho Diwei,
Kim Yongeun,
Bhatt Uditi,
Bond Charles S.,
Hool Livia,
Hurley Laurence H.,
Mergny JeanLouis,
Fear Mark,
Wood Fiona,
Iyer Swaminathan K.,
Smith Nicole M.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13658
Subject(s) - chemistry , g quadruplex , transforming growth factor , microbiology and biotechnology , fibroblast , cancer research , biophysics , stress (linguistics) , biochemistry , medicine , biology , dna , in vitro , philosophy , linguistics
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 Ca 2+ 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.