title: The role and mechanisms of action of SIRT6 in the suppression of postoperative epidural scar formation.
abstract: In order to investigate the role which sirtuin-6 (SIRT6) plays in lumbar spinal epidural fibrosis (EF) and scar formation in vitro and in vivo, SIRT6 and transforming growth factor β (TGF‑β) protein levels in the lumbar disc of patients were detected using western blotting in patients who had undergone a laminectomy. The results demonstrated that SIRT6 expression was significantly reduced in the lumbar discs of patients in whom an epidural scar had formed, but the expression pattern of TGF-β2 was much higher. Subsequently, a pcDNA‑SIRT6 expression vector was constructed and transfected into the primary fibroblasts isolated from the epidural scars. Flow cytometric and MTT analyses indicated that overexpression of SIRT6 suppressed the proliferation of the fibroblasts, and TGF‑β2 and interleukin-1α expression, as well as collagen type I (Col I) production. The results of bioinformatics and molecular biological analyses demonstarted that TGF‑β2 was a target of microRNA-21 (miR-21) and SIRT6 overexpression suppressed the levels of TGF-β2 through promoting the expression of miR-21. Finally, by injecting the pcDNA-SIRT6 vector, it was possible to observe that SIRT6 suppressed EF and epidural scar formation in vivo. In conclusion, we noted that SIRT6 suppressed EF and epidural scar formation in vitro and in vivo. It was also noted that SIRT6 overexpression suppressed TGF-β2 levels by promoting the expression of miR-21.
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lei
authors.affiliation: Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004388:Dura Mater / Q000378:metabolism* / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism; D007796:Laminectomy; D035683:MicroRNAs / Q000235:genetics; D011183:Postoperative Complications; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D014981:Xenopus
chemical_list: D053582:Interleukin-1alpha; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D053781:Transforming Growth Factor beta2; C516592:SIRT6 protein, human; D037761:Sirtuins