Leptin Activates RhoA/ROCK Pathway to Induce Cytoskeleton Remodeling in Nucleus Pulposus Cells
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摘要Hyperleptinemia is implicated in obesity-associated lumbar disc degeneration. Nevertheless, the effect of leptin on the intracellular signaling of nucleus pulposus cells is not clear. The current study sought to delineate the possible involvement of the RhoA/ROCK pathway in leptin-mediated cytoskeleton reorganization in nucleus pulposus cells. Nucleus pulposus cells isolated from scoliosis patients were treated with 10 ng/mL of leptin. Fluorescent resonance energy transfer analysis was used to determine the activation of RhoA signaling in nucleus pulposus cells. The protein expression of LIMK1 and cofilin-2 were analyzed by western blot analysis. F-actin cytoskeletal reorganization was assessed by rhodamine-conjugated phalloidin immunoprecipitation. Leptin induced F-actin reorganization and stress fiber formation in nucleus pulposus cells, accompanied by localized RhoA activation and phosphorylation of LIMK1 and cofilin. The RhoA inhibitor C3 exoenzyme or the ROCK inhibitor Y-27632 potently attenuated the effects of leptin on F-actin reorganization and stress fiber formation. Both inhibitors also prevented leptin-induced phosphorylation of LIMK1 and cofilin-2. Our study demonstrated that leptin activated the RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in nucleus pulposus cells. These findings may provide novel insights into the pathogenic mechanism of obesity-associated lumbar disc degeneration.
著者Li Z, Liang JQ, Wu WKK, Yu X, Yu J, Weng XS, Shen JX
期刊名稱International Journal of Molecular Sciences
出版年份2014
月份1
日期1
卷號15
期次1
出版社MDPI AG
頁次1176 - 1188
國際標準期刊號1661-6596
語言英式英語
關鍵詞cytoskeleton; disc degeneration; F-actin; fluorescent resonance energy transfer (FRET); leptin
Web of Science 學科類別Biochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; CHEMISTRY, MULTIDISCIPLINARY

上次更新時間 2021-23-02 於 00:17