title: An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs.
abstract: BACKGROUND
  The skin is constantly exposed and responds to a wide range of biomechanical cues. The mechanobiology of skin has already been known and applied by clinicians long before the fundamental molecular mechanisms of mechanotransduction are elucidated.
  
  
  METHODS
  Despite increasing knowledge on the mediators of biomechanical signaling such as mitogen-associated protein kinases, Rho GTPases or FAK-ERK pathways, the key elements of mechano-responses transcription factors, and mechano-sensors remain unclear. Recently, canonical biochemical components of Hippo and Wnt signaling pathway YAP and β-catenin were found to exhibit undefined mechanical sensitivity. Mechanical forces were identified to be the dominant regulators of YAP/TAZ activity in a multicellular context. Furthermore, different voltage or ligand sensitive ion channels in the cell membrane exhibited their mechanical sensitivity as mechano-sensors. Additionally, a large number of microRNAs have been confirmed to regulate cellular behavior and contribute to various skin disorders under mechanical stimuli. Mechanosensitive (MS) microRNAs could not only be activated by distinct mechanical force pattern, but also responsively target MS sensors such as e-cadherin and cytoskeleton constituent RhoA.
  
  
  CONCLUSIONS
  Thus, a comprehensive understanding of this regulatory network of cutaneous mechanotransduction will facilitate the development of novel approaches to wound healing, hypertrophic scar formation, skin regeneration, and the progression or initiation of skin diseases.
authors: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, wangjing80s@163.com.
authors: Jing
authors: J
authors: Wang
authors: Yifan
authors: Y
authors: Zhang
authors: Ning
authors: N
authors: Zhang
authors: Chuandong
authors: C
authors: Wang
authors: Tanja
authors: T
authors: Herrler
authors: Qingfeng
authors: Q
authors: Li
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D005786:Gene Expression Regulation; D000090683:Hippo Signaling Pathway; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000235:genetics* / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012867:Skin / Q000378:metabolism*; D012871:Skin Diseases / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D014945:Wound Healing / Q000235:genetics; D000091102:YAP-Signaling Proteins; D051176:beta Catenin / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007473:Ion Channels; D035683:MicroRNAs; D010750:Phosphoproteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D051176:beta Catenin; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D017346:Protein Serine-Threonine Kinases