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Caveolin-1 controls hyperresponsiveness to mechanical stimuli and fibrogenesis-associated RUNX2 activation in keloid fibroblasts

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Chao-Kai Hsu ; Hsi-Hui Lin ; Hans I-Chen Harn ; Rei Ogawa ; Yang-Kao Wang ; Yen-Ting Ho ; Wan-Rung Chen ; Yi-Chao Lee ; Julia Yu-Yun Lee ; Shyh-Jou Shieh ; Chao-Min Cheng ; John A. McGrath ; Ming-Jer Tang

Original languageEnglish
JournalJournal of Investigative Dermatology
Early online date9 Sep 2017
DOIs
StateE-pub ahead of print - 9 Sep 2017

King's Authors

Abstract

Keloids are pathological scars characterized by excessive extracellular matrix production that are prone to form in body sites with increased skin tension. Caveolin-1 (CAV1), the principal coat protein of caveolae, has been associated with the regulation of cell mechanics, including cell softening and loss of stiffness sensing ability in NIH3T3 fibroblasts. Although CAV1 is present in low amounts in keloid fibroblasts (KFs), the causal association between CAV1 downregulation and its aberrant responses to mechanical stimuli remain unclear. In this study, atomic force microscopy showed that KFs were softer than normal fibroblasts with a loss of stiffness sensing. The decrease of CAV1 contributed to the hyperactivation of fibrogenesis-associated RUNX2, a transcription factor germane to osteogenesis/chondrogenesis, and increased migratory ability in KFs. Treatment of KFs with trichostatin A (TSA), which increased the acetylation level of histone H3, increased CAV1 and decreased RUNX2 and fibronectin. TSA treatment also resulted in cell stiffening and decreased migratory ability in KFs. Collectively, these results suggest a novel role for CAV1 downregulation in linking the aberrant responsiveness to mechanical stimulation and extracellular matrix accumulation with the progression of keloids, findings that may lead to new developments in the prevention and treatment of keloid scarring.

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