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  2. Upregulation of HSP72 attenuates tendon adhesion by regulating fibroblast proliferation and collagen production via blockade of the STAT3 signaling pathway

Upregulation of HSP72 attenuates tendon adhesion by regulating fibroblast proliferation and collagen production via blockade of the STAT3 signaling pathway

  • Cell Signal. 2020 Jul;71:109606. doi: 10.1016/j.cellsig.2020.109606.
Zhengqi Pan 1 Qinfen Wu 2 Zhe Xie 3 Qiang Wu 4 Xinti Tan 5 Xin Wang 6
Affiliations

Affiliations

  • 1 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Department of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China.
  • 2 Department of Surgery, the Hospital of Hubei Provincial Government, Wuhan 430071, PR China.
  • 3 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China.
  • 4 Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, PR China.
  • 5 Department of Histology and Embryology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, PR China.
  • 6 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China. Electronic address: [email protected].
Abstract

The proliferation of fibroblasts creates an environment favoring post-operative tendon adhesion, but targeted therapy of this pathology remains in its infancy. In this study, we explored the effect of heat shock protein 72 (HSP72), a major inducible member of the heat shock protein family that can protect cells against many cellular stresses including heat shock, on fibroblast proliferation in tendon adhesion, with its underlying mechanisms investigated. HSP72 expression was examined in an established rat model of tendon injury using RT-qPCR and immunoblot analysis. After conducting ectopic expression and depletion experiments in fibroblast NIH3T3 cells, we determined the effects of HSP72 on the expression of α-SMA and STAT3 signaling pathway-related genes, fibroblast proliferation, as well as collagen production. The mRNA (65.46%) and protein (63.65%) expression of HSP72 was downregulated in the rat model of tendon injury. The in vitro experiments revealed that overexpression of HSP72 inhibited fibroblast proliferation (42.57%) and collagen production (45.60%), as well as reducing α-SMA expression (42.49%) and the extent of STAT3 phosphorylation (55.46%). Moreover, we observed that HSP72 overexpression reduced inflammation as well as the number of inflammatory cell infiltration and fibroblasts in vivo. Furthermore, the inhibited extent of STAT3 phosphorylation contributed to the impaired fibroblast proliferation and collagen production evoked by upregulated HSP72. In summary, the present study unveils an inhibitory role of HSP72 in tendon adhesion via inactivation of the STAT3 signaling pathway. This finding may enable the development of new therapeutic strategies for the prevention against tendon adhesion.

Keywords

Collagen production; Fibroblast proliferation; Heat shock protein 72; Signal transducer and activator of transcription; Tendon adhesion.

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