Fibroblast‐specific Stat1 deletion enhances the myofibroblast phenotype during tissue repair

Abstract

Signal transducer and activator of transcription 1 (Stat1) is a ubiquitously expressed latent transcription factor that is activated by many cytokines and growth factors. Global Stat1 knockout mice are prone to chemical‐induced lung and liver fibrosis, suggesting roles for Stat1 in tissue repair. However, the importance of Stat1 in fibroblast‐mediated and vascular smooth muscle cell (VSMC)‐mediated injury response has not been directly evaluated in vivo. Here, we focused on two models of tissue repair in conditional Stat1 knockout mice: excisional skin wounding in mice with Stat1 deletion in dermal fibroblasts, and carotid artery ligation in mice with global Stat1 deletion or deletion specific to VSMCs. In the skin model, dermal wounds closed at a similar rate in mice with fibroblast Stat1 deletion and controls, but collagen and α‐smooth muscle actin (αSMA) expression were increased in the mutant granulation tissue. Cultured Stat1 −/− and Stat1 +/− dermal fibroblasts exhibited similar αSMA+ stress fiber assembly, collagen gel contraction, proliferation, migration, and growth factor‐induced gene expression. In the artery ligation model, there was a significant increase in fibroblast‐driven perivascular fibrosis when Stat1 was deleted globally. However, VSMC‐driven remodeling and neointima formation were unchanged when Stat1 was deleted specifically in VSMCs. These results suggest an in vivo role for Stat1 as a suppressor of fibroblast mediated, but not VSMC mediated, injury responses, and a suppressor of the myofibroblast phenotype.

Comprehensive analysis of lncRNA and miRNA expression profiles and ceRNA network construction in negative pressure wound therapy

“…STAT1 can promote apoptosis and inflammation (40). Moreover, Medley et al found that STAT1 plays a role in wound repair as a fibroblastmediated inhibitor (41). Along with previous studies, our findings indicate that STAT1 may participate in wound repair through the inflammatory process and the regulation of fibroblasts.…”

Retracted: The role of hyaluronic acid and amino acid against the aging of the human skin: A clinical and histological study

“…4 Actually, the fibroblast-myofibroblast-fibrocyte complex is only one element in a much larger chessboard, which includes other components, both cellular (endothelium of blood and lymphatic vessels, monocyte-macrophages, lymphocytes, nerve ganglia, etc) and noncellular (extracellular matrix and others) and their anabolic processes must be continually balanced by catabolic processes and by cellular reprocessing, under the control of signal molecules (from free radicals to cytokines and up to growth factors). 5,6 In other words, given the structural and functional complexity of the skin at molecular level, it is clear that fibroblast stimulation alone may be inadequate to prevent or treat the imperfections without an "integrated" approach. In the field of esthetic medicine, an important fact is that fragments of hyaluronic acid between 20 and 30 monomers activate the fibroblasts by binding to CD44 receptors and thus the production of reticular collagen type III.…”

IFN-α-2b Reduces Postoperative Arthrofibrosis in Rats by Inhibiting Fibroblast Proliferation and Migration through STAT1/p21 Signaling Pathway

“…In the skin model, the expression of collagen and α-SMA in the granulation tissue around the wound of mice with fibroblast STAT1 gene defects increased, and the perivascular fibrosis increased significantly. These results indicated that STAT1 plays a role in tissue repair [33]. As a key element of IFN-α-2b signal transduction, the function of STAT1 is mainly determined by its phosphorylation state.…”