@article{a2779010adfb4a8a93729b32adface1e,
title = "TGF-β-induced fibrotic stress increases G-quadruplex formation in human fibroblasts",
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.",
keywords = "G-quadruplex, G-quartet, G-tetraplex, G4 DNA, Scar formation",
author = "Priyanka Toshniwal and Michelle Nguyen and Aurore Gu{\'e}din and Helena Viola and Diwei Ho and Yongeun Kim and Uditi Bhatt and Bond, {Charles S.} and Livia Hool and Hurley, {Laurence H.} and Mergny, {Jean Louis} and Mark Fear and Fiona Wood and Iyer, {Swaminathan K.} and Smith, {Nicole M.}",
note = "Funding Information: The authors thank S. Balasubramanian for his gift of pSANG10‐3F‐BG4, Pharmaxis Ltd for PXS64, and Pari Takle for her work on primary human normal fibroblasts. The National Health and Medical Research Council, the Neurotrauma Research Program, the Australian Research Council, the National Heart Foundation of Australia, the National Institute of Health (NIH) award R01CA177585 and the Raine Medical Research Foundation supported this research. The authors acknowledge the facilities and the scientific and technical assistance of the Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, a facility funded by the University, State and Commonwealth Governments. Funding Information: The authors thank S. Balasubramanian for his gift of pSANG10-3F-BG4, Pharmaxis Ltd for PXS64, and Pari Takle for her work on primary human normal fibroblasts. The National Health and Medical Research Council, the Neurotrauma Research Program, the Australian Research Council, the National Heart Foundation of Australia, the National Institute of Health (NIH) award R01CA177585 and the Raine Medical Research Foundation supported this research. The authors acknowledge the facilities and the scientific and technical assistance of the Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, a facility funded by the University, State and Commonwealth Governments. Publisher Copyright: {\textcopyright} 2019 Federation of European Biochemical Societies",
year = "2019",
month = nov,
day = "1",
doi = "10.1002/1873-3468.13658",
language = "English (US)",
volume = "593",
pages = "3149--3161",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "John Wiley and Sons Inc.",
number = "22",
}