title: Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-β/Smad signaling in hypertrophic scar fibroblasts.
abstract: The transforming growth factor-β1 (TGF-β)-mediated signaling pathway is believed to be closely associated with wound healing and scar formation, in which TRAP1-like protein (TLP) plays a role in regulating the balance of Smad2 vs. Smad3 signaling. Our previous study revealed the relation between TLP and collagen synthesis in normal human skin fibroblasts. Here, we present a detailed analysis of the effects of TLP on the process of hypertrophic scar formation and contraction. To explore and verify a contribution of TLP to the pathological mechanism of hypertrophic scar fibroblasts (HSFb), we constructed lentiviral vectors that either overexpressed TLP or encoded small hairpin RNAs (shRNAs) targeting TLP, then we transfected them into HSFb. TLP knockdown in HSFb resulted in reduced levels of cell contraction, type I and type III collagen mRNA transcripts and protein expression, and higher levels of fibronectin (FN) compared to control groups. In addition, knockdown of TLP promoted the phosphorylation of Smad3 but repressed Smad2 and Erk-1/2 phosphorylation in human hypertrophic scar fibroblasts compared to control groups. The reduction of TLP did not interfere with HSF proliferative ability, but exogenous TLP cooperated with TGF-β1 to increase cell viability. Together, our findings demonstrate evidence for a contribution of TLP expression in hypertrophic scar formation and contraction.
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Department of Pediatric Surgery, Shanghai Children's Medical Center, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors: X
authors: X
authors: Wang
authors: Department of Pediatric Surgery, Shanghai Children's Medical Center, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors: J
authors: J
authors: Chu
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors: C J
authors: CJ
authors: Wen
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors: S B
authors: SB
authors: Fu
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors: Y L
authors: YL
authors: Qian
authors: Department of Anatomy, Institutes of Medical Sciences, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Y
authors: Y
authors: Wo
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: wangchen2369@163.com.
authors: C
authors: C
authors: Wang
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: wangdanru@126.com.
authors: D R
authors: DR
authors: Wang
mesh_terms: D000071183:Autophagy-Related Proteins; D049109:Cell Proliferation; D017439:Cicatrix, Hypertrophic / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C485791:VPS39 protein, human; D033921:Vesicular Transport Proteins
keywords: Fibrosis; Hypertrophic scar fibroblasts (HSFb); TRAP1-like protein (TLP)