title: Changes in tension regulates proliferation and migration of fibroblasts by remodeling expression of ECM proteins.
abstract: Wound healing is a complicated but highly organized process in which cell migration and proliferation are actively involved. However, the process by which mechanical stretch regulates the proliferation and migration of human skin fibroblasts (HFs) and keratinocytes is poorly understood. Using a house built mechanical stretch device, we examined the HFs extracellular matrix (ECM) components changes under non-stretch, static stretch or cyclic stretch conditions. We further investigated the changes in ECM component protein expression levels in keratinocytes and analyzed the effects of individual ECM component on keratinocyte proliferation and migration. Particularly, the roles of calcium/calmodulin-dependent serine protein kinase (CASK) in the HF proliferation under cyclic stretch were investigated. Cyclic stretch suppressed HF proliferation compared with HFs without stretch or with static stretch. Cyclic stretch also led to a significant reduction in the levels of collagen I and a marked increase of fibronectin in HFs ECM. By contrast, collagen I levels increased and fibronectin levels decreased in response to non-stretch and static stretch conditions. After cyclic stretch, the proliferation of keratinocytes was inhibited by the cyclic stretch-induced ECM in HFs. The inoculation of keratinocytes with single ECM component suggested that collagen I was more capable of inducing cell proliferation than fibronectin, while it had less impact on cell migration compared with fibronectin. Furthermore, cyclic stretch induced by proliferation inhibition was associated with altered integrin β1-CASK signal pathway. The present results demonstrated the existence of HF-ECM-keratinocyte 'cross-talk' in cutaneous tissues. Thus, the integrin β1-CASK signal pathway in HFs may be involved in the outside-in signal transduction of extracellular stretch and the altered ECM component expression.
authors: Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China; Central Laboratory, The People's Hospital of Guizhou Province, Guiyang, Guizhou 550002, P.R. China.
authors: Minmin
authors: M
authors: Jiang
authors: Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China; National Key Laboratory of Trauma and Burns and Chongqing Key Laboratory of Disease Proteomics, Chongqing 400038, P.R. China.
authors: Juhui
authors: J
authors: Qiu
authors: Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China; National Key Laboratory of Trauma and Burns and Chongqing Key Laboratory of Disease Proteomics, Chongqing 400038, P.R. China.
authors: Lingling
authors: L
authors: Zhang
authors: Key Laboratory of Microgravity (National Microgravity Laboratory) and Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, P.R. China.
authors: Dongyuan
authors: D
authors: Lü
authors: Key Laboratory of Microgravity (National Microgravity Laboratory) and Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, P.R. China.
authors: Mian
authors: M
authors: Long
authors: Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China; National Key Laboratory of Trauma and Burns and Chongqing Key Laboratory of Disease Proteomics, Chongqing 400038, P.R. China; Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Li
authors: L
authors: Chen
authors: Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China; National Key Laboratory of Trauma and Burns and Chongqing Key Laboratory of Disease Proteomics, Chongqing 400038, P.R. China.
authors: Xiangdong
authors: X
authors: Luo
keywords: calcium/calmodulin-dependent serine protein kinase; extracellular matrix; human skin fibroblast; integrin; keratinocyte; mechanical stretch