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- 저자 : Wang Weishun (검색결과 1 건)
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Wang Haoran,Wu Tao,Hua Feng,Sun Jinpeng,Bai Yunfeng,Wang Weishun,Liu Jun,Zhang Mingshun 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.3
BACKGROUND: Recent evidence suggests that IL-33, a novel member of the IL-1b family, is involved in organ fibrosis. However, the roles of IL-33 and its receptor ST2 in epidural fibrosis post spine operation remain elusive. METHODS: A mouse model of epidural fibrosis was established after laminectomy. IL-33 in the wound tissues post laminectomy was measured with Western blotting, ELISA and immunoflurosence imaging. The fibroblast cell line NIH- 3T3 and primary fibroblasts were treated with IL-33 and the mechanisms of maturation of fibroblasts into myofibroblasts were analyzed. To explore roles of IL-33 and its receptor ST2 in vivo, IL-33 knockout (KO) and ST2 KO mice were employed to construct the model of laminectomy. The epidural fibrosis was evaluated using H&E and Masson staining, western-blotting, ELISA and immunohistochemistry. RESULTS: As demonstrated in western blotting and ELISA, IL-33 was increased in epidural wound tissues post laminectomy. The immunoflurosence imaging revealed that endothelial cells (CD31?) and fibroblasts (a-SAM?) were major producers of IL-33 in the epidural wound tissues. In vitro, IL-33 promoted fibroblast maturation, which was blocked by ST2 neutralization antibody, suggesting that IL-33-promoted-fibroblasts maturation was ST2 dependent. Further, IL-33/ ST2 activated MAPK p38 and TGF-b pathways. Either p38 inhibitor or TGF-b inhibitor decreased fibronectin and a-SAM production from IL-33-treated fibroblasts, suggesting that p38 and TGF-b were involved with IL-33/ST2 signal pathways in the fibroblasts maturation. In vivo, IL-33 KO or ST2 KO decreased fibronectin, a-SMA and collagen deposition in the wound tissues of mice that underwent spine surgery. In addition, TGF-b1 was decreased in IL-33 KO or ST2 KO epidural wound tissues. CONCLUSION: In summary, IL-33/ST2 promoted fibroblast differentiation into myofibroblasts via MAPK p38 and TGFb in a mouse model of epidural fibrosis after laminectomy.
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