Leptin Activates RhoA/ROCK Pathway to Induce Cytoskeleton Remodeling in Nucleus Pulposus Cells
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AbstractHyperleptinemia 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.
All Author(s) ListLi Z, Liang JQ, Wu WKK, Yu X, Yu J, Weng XS, Shen JX
Journal nameInternational Journal of Molecular Sciences
Year2014
Month1
Day1
Volume Number15
Issue Number1
PublisherMDPI AG
Pages1176 - 1188
ISSN1661-6596
LanguagesEnglish-United Kingdom
Keywordscytoskeleton; disc degeneration; F-actin; fluorescent resonance energy transfer (FRET); leptin
Web of Science Subject CategoriesBiochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; CHEMISTRY, MULTIDISCIPLINARY

Last updated on 2021-15-04 at 23:55