Abstract
BackgroundHypertrophic scars are pathologic proliferations of the dermal skin layer resulting from excessive collagen deposition during the healing process of cutaneous wounds. Current research suggests that the TGF-β/Smad signaling pathway is closely associated with normal scar and hypertrophic scar formation. TRAP-1-like protein (TLP), a cytoplasmic protein, has been reported to efficiently regulate Smad2- and Smad3-dependent signal expression in the TGF-β pathway. The relationship between TLP and Type I/III collagen (Col I/III) synthesis explored in the present study provides an effective target for wound healing and gene therapy of hypertrophic scarring.ObjectiveTo investigate the effects of TLP on collagen synthesis in human dermal fibroblasts. MethodsLentiviral vectors encoding TLP was constructed to transfect fibroblasts derived from normal human skin. The expression of Col I/III and phosphorylation of Smad2 and Smad3 in fibroblasts were examined after TLP treatment. In addition, the comparison of TLP expression in normal skin tissues and in hypertrophic scar tissues was performed, and the effect of TLP on cell viability was analyzed by MTT assay.ResultsTLP expression in hypertrophic scar tissue was markedly higher than in normal skin tissue. The Real Time PCR and Western blot test results both revealed that the synthesis of Col I/III was positively correlated with the expression of TLP. TLP also facilitate Smad2 phosphorylation while, conversely, inhibiting Smad3 phosphorylation. TLP may play a cooperative role, along with the cytokine TGF-β1, in improving the overall cell viability of skin fibroblasts.ConclusionsTLP likely acts as a molecular modulator capable of altering the balance of Smad3- and Smad2-dependent signaling through regulation of phosphorylation, thus facilitating collagen synthesis in fibroblasts. Based on genetic variation in TLP levels in different tissues, these results suggest that TLP plays a key role in the process of TGF-β1/Smad3 signaling that contributes to wound healing and genesis of pathologic scars.
Highlights
Scar, the inevitable complication of wound healing, often incurs excessive proliferation of fibrous tissue with the potential to result in deformity of appearance, paraesthesia, and even organ dysfunctions, leading to significant psychological diseases for burn survivors
The Real Time polymerase chain reaction (PCR) and Western blot test results both revealed that the synthesis of Col I/III was positively correlated with the expression of TRAP-1-like protein (TLP)
TLP likely acts as a molecular modulator capable of altering the balance of Smad3- and Smad2-dependent signaling through regulation of phosphorylation, facilitating collagen synthesis in fibroblasts
Summary
The inevitable complication of wound healing, often incurs excessive proliferation of fibrous tissue with the potential to result in deformity of appearance, paraesthesia, and even organ dysfunctions, leading to significant psychological diseases for burn survivors. Hypertrophic scars may result from abnormal fibrous wound healing that has exhibited reduced or absent tissue repairment and regeneration regulating mechanisms. Deepened understanding of the TGF-b signal transduction pathway has led increasing investigators to attempt at the inhibition of TGF-b transduction at various levels Examples of these therapies include treatment with TGF-b antagonists [4], truncated TGF-b1 receptors [5], compounds capable of blocking the Smad signaling pathway [6], induced overexpression of Smad7 [7], and glucocorticoids that block intranuclear signals [8]. Some therapies have even been shown to be adverse to wound healing, such as overinhibition of the fibronectin synthesis These effects have been puzzling investigators over the past decades by suggesting the existence of an undetermined target protein possessing specific and important biological effects on signaling pathways. The relationship between TLP and Type I/III collagen (Col I/III) synthesis explored in the present study provides an effective target for wound healing and gene therapy of hypertrophic scarring
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
