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Updated: Jun 4, 2026
09:40
Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
[PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski]
Gong-bo Li1, Jun Li, Yi-jun Zeng
1Department of Biochemistry and Molecular Biology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Sheng Li Xue Bao : [Acta Physiologica Sinica]
|February 23, 2011
Summary
Peroxisome proliferator-activated receptor γ (PPARγ) activation regulates c-Ski, a TGFβ/smad pathway repressor, offering a new therapeutic target for atherosclerosis (AS). This study reveals c-Ski as a PPARγ target gene involved in anti-atherosclerotic effects.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Signal Transduction
Background:
- Atherosclerosis (AS) pathogenesis involves the TGFβ/smad pathway.
- Peroxisome proliferator-activated receptor γ (PPARγ) activation plays a role in modulating AS.
- c-Ski acts as a repressor of the TGFβ/smad pathway.
Purpose of the Study:
- To investigate the regulation of c-Ski by PPARγ in a rat AS model and cultured vascular smooth muscle cells (VSMCs).
- To explore the potential of c-Ski as a target for anti-atherosclerotic therapies.
Main Methods:
- Real-time PCR and Western blot to detect c-Ski mRNA and protein expression in vivo and in vitro.
- Treatment with PPARγ agonist rosiglitazone and antagonist GW9662.
- Investigation of VSMC proliferation and collagen secretion after c-Ski transfection.
- NUBIScan analysis and luciferase reporter gene assay to elucidate the mechanism.
Main Results:
- c-Ski expression was down-regulated in AS lesions in vivo.
- c-Ski transfection suppressed VSMC proliferation and collagen secretion.
- Rosiglitazone upregulated c-Ski expression in VSMCs, an effect blocked by GW9662.
- PPARγ binding sites were identified in the c-Ski promoter region, and rosiglitazone increased c-Ski reporter gene activity.
Conclusions:
- c-Ski is a novel target gene of PPARγ.
- PPARγ activation upregulates c-Ski, contributing to its anti-atherosclerotic effects.
- Targeting the PPARγ-c-Ski axis may offer a therapeutic strategy for atherosclerosis.
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