Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; International Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
International Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
J Dermatol Sci. 2018 Jun;90(3):232-240. doi: 10.1016/j.jdermsci.2018.03.004. Epub 2018 Mar 8.
Mechanical forces are known to regulate homeostasis of the skin and play a role in the pathogenesis of skin diseases. The epidermis consists of keratinocytes that are tightly adhered to each other by cell junctions. Defects in keratins or desmosomal/hemidesmosomal proteins lead to the attenuation of mechanical strength and formation of intraepidermal blisters in the case of epidermolysis bullosa simplex. The dermis is rich in extracellular matrix, especially collagen, and provides the majority of tensile force in the skin. Keloid and hypertrophic scar, which is the result of over-production of collagen by fibroblasts during the wound healing, are associated with extrinsic tensile forces and changes of intrinsic mechanical properties of the cell. Increasing evidences shows that stiffness of the skin environment determines the regenerative ability during wound healing process. Mechanotransduction pathways are also involved in the morphogenesis and cyclic growth of hair follicles. The development of androgenetic alopecia is correlated to tensile forces generated by the fibrous tissue underlying the scalp. Acral melanoma predominantly occurs in the weight-bearing area of the foot suggesting the role of mechanical stress. Increased dermal stiffness from fibrosis might be the cause of recessive dystrophic epidermolysis bullosa associated squamous cell carcinoma. Strategies to change the mechanical forces or modify the mechanotransduction signals may lead to a new way to treat skin diseases and promote skin regeneration.
机械力被认为可以调节皮肤的内稳态，并在皮肤疾病的发病机制中发挥作用。表皮由角朊细胞组成，这些细胞通过细胞连接紧密地连接在一起。角蛋白或桥粒/半桥粒蛋白的缺陷会导致机械强度减弱，并在单纯性表皮松解症中形成表皮内水疱。真皮富含细胞外基质，尤其是胶原，为皮肤提供大部分拉伸力。瘢痕疙瘩和增生性瘢痕是成纤维细胞在伤口愈合过程中过度产生胶原的结果，它们与外在拉伸力和细胞固有机械特性的变化有关。越来越多的证据表明，皮肤环境的硬度决定了伤口愈合过程中的再生能力。机械转导途径也参与毛囊的形态发生和周期性生长。雄激素性脱发的发展与头皮下纤维组织产生的张力有关。肢端黑色素瘤主要发生在足部承重区域，提示机械应力的作用。纤维化导致的真皮硬度增加可能是隐性营养不良性大疱性表皮松解症相关鳞状细胞癌的原因。改变机械力或修饰机械转导信号的策略可能为治疗皮肤疾病和促进皮肤再生开辟新途径。
