Endogenous peptide LYENRL prevents the activation of hypertrophic scar-derived fibroblasts by inhibiting the TGF-β1/Smad pathway.
Hypertrophic scar formation is a fibroproliferative disorder caused by abnormal wound healing. At present, there are limited treatment strategies for hypertrophic scars. In this study, we identified an endogenous peptide, LYENRL, through peptidomics screening that is downregulated in scar skin tissues. The peptide exhibited concentration dependent inhibitory effects on the proliferation, migration and extracellular matrix (ECM) production of scar fibroblasts. By eukaryotic transcriptome sequencing analysis, we noted that LYENRL downregulated gene sets in scar fibroblasts were associated with the transforming growth factor-β (TGF-β) signaling pathway. Further experiments revealed that LYENRL was able to inhibit the activation of TGF-β1/Smad signaling and TGF-β1-induced activation of scar fibroblasts at the source by blocking the binding of AP-1 to the corresponding region of the Tgfb1 promoter, which in turn inhibited gene expression of Tgfb1. Taken together, we concluded that the effects of LYENRL on scar fibroblasts make it a potential peptide drug for hypertrophic scar treatment.
['Ji|Xiaojun|X|', 'Tang|Zhe|Z|', 'Shuai|Weiwei|W|', 'Zhang|Zhirui|Z|', 'Li|Jingyun|J|', 'Chen|Ling|L|', 'Cao|Jing|J|', 'Yin|Wu|W|']
D000199:Actins D002460:Cell Line D002478:Cells, Cultured D017439:Cicatrix, Hypertrophic D015536:Down-Regulation D005109:Extracellular Matrix D005260:Female D005347:Fibroblasts D006801:Humans D010455:Peptides D061251:Primary Cell Culture D015398:Signal Transduction D012867:Skin D051785:Smad Proteins D051900:Smad3 Protein D016212:Transforming Growth Factor beta D053773:Transforming Growth Factor beta1
Endogenous peptide LYENRL Fibroblasts TGF-β1/Smad Hypertrophic scars