| 9 | Fibromodulin reduces scar formation in adult cutaneouswounds by eliciting a fetal-like phenotype显示文摘Blocking transforming growth factor(TGF)β1 signal transduction has been a central strategy for scar reduction;however,this approach appears to be minimally effective.Here,we show that fibromodulin(FMOD),a 59-kD small leucine-rich proteoglycan critical for normal collagen fibrillogenesis,significantly reduces scar formation while simultaneously increasing scar strength in both adult rodent models and porcine wounds,which simulate human cutaneous scar repair.Mechanistically,FMOD uncouples promigration/contraction cellular signals from pro-fibrotic signaling by selectively enhancing SMAD3-mediated signal transduction,while reducing AP-1-mediated TGFβ1 auto-induction and fibrotic extracellular matrix accumulation.Consequently,FMOD accelerates TGFβ1-responsive adult fibroblast migration,myofibroblast conversion,and function.Furthermore,our findings strongly indicate that,by delicately orchestrating TGFβ1 activities rather than indiscriminately blocking TGFβ1,FMOD elicits fetal-like cellular and molecular phenotypes in adult dermal fibroblasts in vitro and adult cutaneous wounds in vivo,which is a unique response of living system undescribed previously.Taken together,this study illuminates the signal modulating activities of FMOD beyond its structural support functions,and highlights the potential for FMOD-based therapies to be used in cutaneous wound repair. | Zhong Zheng Aaron W James Chenshuang Li Wenlu Jiang Joyce Z Wang Grace X Chang Kevin S Lee Feng Chen Emily A Berthiaume Yao Chen Hsin Chuan Pan Eric C Chen Weiming Li Zhihe Zhao Xinli Zhang Kang Ting Chia Soo | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 0 |
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