TGF-β-induced fibrotic stress increases G-quadruplex formation in human fibroblasts

FEBS Letters

article

Priyanka Toshniwal¹  Michelle Nguyen¹  Aurore Guédin²  Helena Viola³  Diwei Ho¹  Yongeun Kim⁴  Uditi Bhatt¹  Charles S. Bond¹  Livia Hool³  Laurence H. Hurley⁴  Jean-Louis Mergny²  Mark Fear⁷  Fiona Wood⁷  Swaminathan K. Iyer¹  Nicole M. Smith¹ 

[1] School of Molecular Sciences, The University of Western Australia;ARNA Laboratory, Université de Bordeaux;School of Human Sciences, The University of Western Australia;College of Pharmacy, University of Arizona;Victor Chang Cardiac Research Institute;Institut Curie, Université Paris Saclay;Fiona Wood Foundation and Burn Injury Research Unit, The University of Western Australia

关键词: G4 DNA;    G-quadruplex;    G-quartet;    G-tetraplex;    Scar formation;   

DOI  :  10.1002/1873-3468.13658

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-b-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 antifibrotic 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.

【 授权许可】

Unknown