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Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-?/Smad signaling pathway.

ABSTRACT: Keloids are a type of aberrant skin scarring characterized by excessive accumulation of collagen and extracellular matrix (ECM), arising from uncontrolled wound healing responses. While typically non-pathogenic, keloids are occasionally regarded as a form of benign tumor. CR6-interacting factor 1 (CRIF1) is a well-known CR6/GADD45-interacting protein, that has both nuclear and mitochondrial functions, and also exerts regulatory effects on cell growth and apoptosis. In this study, cell proliferation, cell migration, collagen production and TGF-? signaling was compared between normal fibroblasts (NFs) and keloid fibroblasts (KFs). Subsequently, the effects of CRIF1 deficiency were investigated in both NFs and KFs. Cell proliferation, cell migration, collagen production and protein expressions of TGF-?, phosphorylation of Smad2 and Smad3 were all found to be higher in KFs compared to NFs. CRIF1 deficiency in NFs and KFs inhibited cell proliferation, migration, and collagen production. In addition, phosphorylation of Smad2 and Smad3, which are transcription factors of collagen, was decreased. In contrast, mRNA expression levels of Smad7 and SMURF2, two important inhibitory proteins of Smad2/3, were increased, suggesting that CRIF1 may regulate collagen production. CRIF1 deficiency decreases the proliferation and migration of KFs, thereby inhibiting their overgrowth via the transforming growth factor-? (TGF-?)/Smad pathway. CRIF1 may therefore represent a potential therapeutic target in keloid pathogenesis.

SUBMITTER: Nagar H

PROVIDER: S-EPMC7804403 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway.

Nagar Harsha H Kim Sungmin S Lee Ikjun I Kim Seonhee S Choi Su-Jeong SJ Piao Shuyu S Jeon Byeong Hwa BH Oh Sang-Ha SH Kim Cuk-Seong CS

Scientific reports 20210112 1

Keloids are a type of aberrant skin scarring characterized by excessive accumulation of collagen and extracellular matrix (ECM), arising from uncontrolled wound healing responses. While typically non-pathogenic, keloids are occasionally regarded as a form of benign tumor. CR6-interacting factor 1 (CRIF1) is a well-known CR6/GADD45-interacting protein, that has both nuclear and mitochondrial functions, and also exerts regulatory effects on cell growth and apoptosis. In this study, cell proliferat ...[more]

PMID: 33436666

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Dataset Information

Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-?/Smad signaling pathway.

Publications

Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway.

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