title: All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats.
abstract: Laminectomy is a widely accepted treatment for lumbar disorders, and epidural fibrosis (EF) is a common complication. EF is thought to cause post-operative pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA) has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The object of this study was to investigate the effects of ATRA on the prevention of EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was demonstrated with cultured fibroblasts count, which comprised of those that were cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2 levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to vehicle (control group). We found that a higher concentration of ATRA (0.1%) achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin-positive cell density, fibroblast density, inflammatory cell density and inflammatory factor expression levels all suggested better outcomes in the 0.1% ATRA rats compared to the other three groups. Presumably, these effects involved ATRA's ability to suppress transforming growth factor (TGF-β1) and interleukin (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)-κB by immunohistochemistry and western blotting for p65 and inhibition of κB (IκBα), respectively. Our findings indicate that topical application of ATRA can inhibit fibroblast proliferation, decrease TGF-β1 and IL-6 expression level, and prevent epidural scar adhesion in rats. The highest concentration employed in this study (0.1%) was the most effective. ATRA suppressed EF through down-regulating NF-κB signaling, whose specific mechanism is suppression of IκB phosphorylation and proteolytic degradation.
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Chao
authors: C
authors: Zhang
authors: School of Medicine, Nankai University, Tianjin 300071, China.
authors: Xiaohong
authors: X
authors: Kong
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Guangzhi
authors: G
authors: Ning
authors: School of Medicine, Nankai University, Tianjin 300071, China.
authors: Zhipin
authors: Z
authors: Liang
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Tongjun
authors: T
authors: Qu
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Feiran
authors: F
authors: Chen
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Daigui
authors: D
authors: Cao
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Tianyi
authors: T
authors: Wang
authors: Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Frödingsgatan 12, 75421 Uppsala, Sweden.
authors: Hari S
authors: HS
authors: Sharma
authors: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: fengsq@hotmail.com.
authors: Shiqing
authors: S
authors: Feng
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D002921:Cicatrix / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004824:Epidural Space / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005355:Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007641:Keratolytic Agents / Q000494:pharmacology*; D007796:Laminectomy / Q000009:adverse effects*; D008159:Lumbar Vertebrae; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D007641:Keratolytic Agents; D016328:NF-kappa B; D014212:Tretinoin
keywords: Epidural fibrosis; Laminectomy; NF-κB signaling pathway; Rat; Retinoic acid