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Leptin activates RhoA/ROCK pathway to induce cytoskeleton remodeling in nucleus pulposus cells
Zheng Li1, Jinqian Liang2, William Ka Kei Wu3
1Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China. kleeo@163.com.
International Journal of Molecular Sciences
|January 21, 2014
Summary
Leptin triggers changes in nucleus pulposus cell structure via the RhoA/ROCK pathway. This cellular mechanism may contribute to obesity-related lumbar disc degeneration.
Area of Science:
- Cell Biology
- Biochemistry
- Orthopedics
Background:
- Hyperleptinemia is linked to obesity-associated lumbar disc degeneration.
- The specific intracellular signaling pathways affected by leptin in nucleus pulposus cells remain unclear.
Purpose of the Study:
- To investigate the role of the RhoA/ROCK pathway in leptin-mediated cytoskeleton reorganization within nucleus pulposus cells.
Main Methods:
- Nucleus pulposus cells were treated with leptin.
- RhoA activation was measured using FRET analysis.
- Protein expression of LIMK1 and cofilin-2 was assessed via Western blot.
- F-actin reorganization was visualized using rhodamine-conjugated phalloidin.
Main Results:
- Leptin induced F-actin reorganization and stress fiber formation.
- Leptin activated RhoA signaling and increased phosphorylation of LIMK1 and cofilin-2.
- Inhibitors of RhoA (C3 exoenzyme) and ROCK (Y-27632) attenuated leptin's effects on cytoskeleton and protein phosphorylation.
Conclusions:
- Leptin activates the RhoA/ROCK/LIMK/cofilin-2 cascade, leading to cytoskeleton reorganization in nucleus pulposus cells.
- This pathway offers potential insights into the pathogenesis of obesity-associated lumbar disc degeneration.
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