Jialiang Chen1, Biwei Zeng, Hangping Yao, Jinghong Xu. 1. Department of Plastic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Abstract
BACKGROUND: Keloid formation is closely related with transforming growth factor (TGF)-β-induced Smad signal transduction. Recent studies have shown that toll-like receptor4 (TLR4) may mediate liver and kidney fibrosis, and activation of TLR7 has anti-scarring effect. The role of TLR4/7 signalling in keloid formation, however, remains unknown. Our previous tests have found that mute Smad4 inhibited scar. We then speculated that keloid may be affected by TLR4/7 through TGF-β-induced Smad signal transduction. OBJECTIVES: The aim of this study was to evaluate effects of TLR4/7 on the TGF-β-induced Smad signal transduction pathway in human keloid, and provide information for the mechanism and therapy of keloid. METHODS: Normal scar samples with normal fibroblasts (NFs) served as control samples and keloid samples with keloid fibroblasts (KFs) served as experiment samples. Expression of collagen, connective tissue growth factor (CTGF), Smad4 and Smad7 and TLR4/7 were tested by immunohistochemistry, reverse transcription polymerase chain reaction (PCR) (RT-PCR) and Western blotting, respectively. RESULTS: Expression of collagen, CTGF, Smad4 and TLR4 increased significantly while expression of Smad7 and TLR7 decreased in KFs while compared to NFs in keloid scar group (KFs), which were decreased in the normal scar group (NFs). However, expression of Smad7 and TLR7 decreased in the keloid scar group (KFs) while compared to the NFs. CONCLUSIONS: TLRs participate in fibrosis of scar tissue through the TLRs-TGF-β-Smads signal pathway. Higher expression of TLR4 in keloid increased expression of TGF-β, CTGF and collagen through the Smad4 signal pathway. Activation of TLR7 or Smad7 may inhibit scar formation.
BACKGROUND: Keloid formation is closely related with transforming growth factor (TGF)-β-induced Smad signal transduction. Recent studies have shown that toll-like receptor4 (TLR4) may mediate liver and kidney fibrosis, and activation of TLR7 has anti-scarring effect. The role of TLR4/7 signalling in keloid formation, however, remains unknown. Our previous tests have found that mute Smad4 inhibited scar. We then speculated that keloid may be affected by TLR4/7 through TGF-β-induced Smad signal transduction. OBJECTIVES: The aim of this study was to evaluate effects of TLR4/7 on the TGF-β-induced Smad signal transduction pathway in human keloid, and provide information for the mechanism and therapy of keloid. METHODS: Normal scar samples with normal fibroblasts (NFs) served as control samples and keloid samples with keloid fibroblasts (KFs) served as experiment samples. Expression of collagen, connective tissue growth factor (CTGF), Smad4 and Smad7 and TLR4/7 were tested by immunohistochemistry, reverse transcription polymerase chain reaction (PCR) (RT-PCR) and Western blotting, respectively. RESULTS: Expression of collagen, CTGF, Smad4 and TLR4 increased significantly while expression of Smad7 and TLR7 decreased in KFs while compared to NFs in keloid scar group (KFs), which were decreased in the normal scar group (NFs). However, expression of Smad7 and TLR7 decreased in the keloid scar group (KFs) while compared to the NFs. CONCLUSIONS: TLRs participate in fibrosis of scar tissue through the TLRs-TGF-β-Smads signal pathway. Higher expression of TLR4 in keloid increased expression of TGF-β, CTGF and collagen through the Smad4 signal pathway. Activation of TLR7 or Smad7 may inhibit scar formation.