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.

中文翻译：

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HSP72 的上调通过阻断 STAT3 信号通路来调节成纤维细胞增殖和胶原蛋白生成，从而减弱肌腱粘附。

成纤维细胞的增殖创造了一个有利于术后肌腱粘连的环境，但这种病理的靶向治疗仍处于起步阶段。在这项研究中，我们探讨了热休克蛋白 72 (HSP72)（热休克蛋白家族的主要诱导型成员，可以保护细胞免受热休克等多种细胞应激）对肌腱粘附中成纤维细胞增殖的影响及其潜在机制调查。使用 RT-qPCR 和免疫印迹分析在已建立的肌腱损伤大鼠模型中检查 HSP72 表达。在成纤维细胞 NIH3T3 细胞中进行异位表达和消耗实验后，我们确定了 HSP72 对 α-SMA 和 STAT3 信号通路相关基因表达、成纤维细胞增殖以及胶原蛋白生成的影响。mRNA (65.46%) 和蛋白质 (63. 65%) HSP72 的表达在肌腱损伤的大鼠模型中被下调。体外实验表明，HSP72的过表达抑制了成纤维细胞增殖（42.57%）和胶原蛋白生成（45.60%），并降低了α-SMA表达（42.49%）和STAT3磷酸化程度（55.46%）。此外，我们观察到 HSP72 过表达减少了炎症以及体内炎症细胞浸润和成纤维细胞的数量。此外，STAT3 磷酸化的抑制程度导致了由上调的 HSP72 引起的成纤维细胞增殖和胶原蛋白生成受损。总之，本研究通过 STAT3 信号通路的失活揭示了 HSP72 在肌腱粘连中的抑制作用。