Int J Biol Sci 2022; 18(4):1347-1362. doi:10.7150/ijbs.67974 This issue

Research Paper

LncRNA-COX2 inhibits Fibroblast Activation and Epidural Fibrosis by Targeting EGR1

Lei Yang1,2,3, Shengnai Zheng4, Dawei Ge4, Mingjie Xia4, Haijun Li1,2,✉, Jian Tang5,✉

1. Taizhou Clinical Medical School of Nanjing Medical University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, China.
2. Department of Orthopedics, Hospital Affiliated 5 to Nantong University, Taizhou, Jiangsu 225300, China.
3. School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
4. Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China.
5. Department of Plastic and Burn Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

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Citation:
Yang L, Zheng S, Ge D, Xia M, Li H, Tang J. LncRNA-COX2 inhibits Fibroblast Activation and Epidural Fibrosis by Targeting EGR1. Int J Biol Sci 2022; 18(4):1347-1362. doi:10.7150/ijbs.67974. Available from https://www.ijbs.com/v18p1347.htm

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Abstract

Graphic abstract

Rationale: Epidural fibrosis is one of the contributors to failed back surgery syndrome (FBSS) with a high incidence of about 80,000 cases per year. The fibrosis spreads from the operative region to the dura mater or the nerve root and results in functional incapacity and pain after laminectomy. Our previous study showed that down-regulation of lncRNA-COX2 is involved in the epidural scar formation. However, it remains unknown whether lncRNA-COX2 participate in the fibroblast activation and epidural fibrogenesis.

Methods: LncRNA-COX2 and EGR1 expression were assessed by qRT-PCR and western blotting. Fibroblasts differentiation, proliferation and migration was determined by Collagen I/ɑ-SMA, 5-ethynyl-2'-deoxyuridine (EdU) and Transwell Assay respectively. Luciferase reporter assay was performed for the verification of target of LncRNA-COX2. Laminectomy was performed to establish the model of epidural fibrosis in mice. Epidural scar was evaluated by hematoxylin and eosin (HE) staining and Masson Trichrome staining.

Results: Based on the result of transcriptome profiling, we found LncRNA-COX2 was significantly decreased in epidural tissues after laminectomy and in activated fibrotic fibroblasts. In vitro, overexpression of LncRNA-COX2 suppressed epidural fibrogenesis by inhibiting fibroblasts differentiation, proliferation and migration. Mechanistically, LncRNA-COX2 functioned as competing endogenous RNA (ceRNA) of EGR1. Gain of LncRNA-COX2 significantly decreased the expression of EGR1 and showed anti-fibrotic effect while EGR1 was markedly increased after loss of LncRNA-COX2. In vivo, LncRNA-COX2 attenuated laminectomy-induced epidural fibrosis in mice.

Conclusion: In summary, the results demonstrated that LncRNA-COX2 showed anti-fibrotic effect by targeting EGR1 and identified LncRNA-COX2 as therapeutic molecule for preventing aberrant epidural fibrosis.

Keywords: LncRNA-COX2, Fibroblast Activation, laminectomy, Epidural Fibrosis, EGR1.