KMID : 1377020220190030577
|
|
Tissue Engineering and Regenerative Medicine 2022 Volume.19 No. 3 p.577 ~ p.588
|
|
IL-33 Promotes ST2-Dependent Fibroblast Maturation via P38 and TGF-¥â in a Mouse Model of Epidural Fibrosis
|
|
Wang Haoran
Wu Tao Hua Feng Sun Jinpeng Bai Yunfeng Wang Weishun Liu Jun Zhang Mingshun
|
|
Abstract
|
|
|
BACKGROUND: Recent evidence suggests that IL-33, a novel member of the IL-1¥â 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 (¥á-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-¥â pathways. Either p38 inhibitor or TGF-¥â inhibitor decreased fibronectin and ¥á-SAM production from IL-33-treated fibroblasts, suggesting that p38 and TGF-¥â were involved with IL-33/ST2 signal pathways in the fibroblasts maturation. In vivo, IL-33 KO or ST2 KO decreased fibronectin, ¥á-SMA and collagen deposition in the wound tissues of mice that underwent spine surgery. In addition, TGF-¥â1 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 TGF-¥â in a mouse model of epidural fibrosis after laminectomy.
|
|
KEYWORD
|
|
Epidural fibrosis, Fibroblast, IL-33, ST2, p38, TGF-¥â1
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|