Upregulation of HSP72 attenuates tendon adhesion by regulating fibroblast proliferation and collagen production via blockade of the STAT3 signaling pathway |
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| Institution: | 1. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;2. Genetics Research Center, University of Social Welfare and Rehabilitation, Tehran, Iran;3. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;4. Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;5. Iranshahr University of Medical Sciences, Iranshahr, Iran;6. Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;7. Student Research Committee and Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran;8. Immunology Research Center, Inflammation and Inflammatory Diseases Division, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;9. Division of Medical Education, Brighton & Sussex Medical School, Brighton, Sussex, UK;10. Division of Pulmonary and Critical Care Medicine, Washington University, School of Medicine, Saint Louis, Missouri;11. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland;1. Department of Orthopedic Surgery, Virginia Commonwealth University, Richmond, VA;1. Department of Pharmacology, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan, PR China;2. Department of Biochemistry, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan, PR China;3. School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, Australia;4. Cardiovascular Division and Lillehei Heart Institute, University of Minnesota, MN, USA;5. Department of Cardiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China;1. Department of Orthopedics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China;2. Central Laboratory, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China;1. Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA;2. Division of Plastic Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;1. Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong Special Administrative Region;2. Hong Kong Jockey Club Sports Medicine and Health Sciences Centre, Chinese University of Hong Kong, Hong Kong Special Administrative Region |
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| 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. |
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