Rosiglitazone inhibits angiotensin II-induced CTGF expression in vascular smooth muscle cells––Role of PPAR-γ in vascular fibrosis

Gao, Dengfeng; Niu, Xiaolin; Hao, Guanghua; Ning, Peng; Wei, Jin; Ning, Ning; Wang, Nanping

doi:10.1016/j.bcp.2006.09.019

Cited by 50 publications

(46 citation statements)

References 52 publications

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“…Besides glucose control, RSG shows diverse therapeutic effects in the regulation of endothelial function, cellular apoptosis, tissue fibrosis, and the control of blood pressure. [28][29][30][31][32] In addition, it limits cardiac hypertrophy in diet-induced hypercholesterolemic rats by the renin-angiotensin system. 16) Furthermore, current evidence suggests that it has beneficial effects on CMCs under oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

The PPARγ Agonist Protects Cardiomyocytes from Oxidative Stress and ApoptosisviaThioredoxin Overexpression

Kim

Park

Song

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 99%

The PPARγ Agonist Protects Cardiomyocytes from Oxidative Stress and ApoptosisviaThioredoxin Overexpression

Kim

Park

Song

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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“…The side effects of thiazolidinediones on bones are thought to be mainly due to the proadipocytic and antiosteoblastogenic effects of these drugs on pluripotent mesenchymal stem cells (Lecka-Czernik et al, 2002;Shockley et al, 2009). However, reduction in ECM production via inhibited TGF-␤1 or CTGF expression may be of equal importance (Peng et al, 2006;Gao et al, 2007) in defining the efficacy of these drugs. The new biological anti-inflammatory and immunomodulatory drugs, such as tumor necrosis factor inhibitors and the interleukin-1 inhibitor anakinra, may also cause adverse side-effects on the ECM, particularly in the skin (Deng et al, 2006;Regula et al, 2008).…”

Section: Deleterious Effects Of Current Drugs On the Extracellularmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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“…As described earlier, 30 protein samples (20 mg) were separated on 12% SDS-PAGE gels and transferred onto a polyvinylidene difluoride membrane (Bio-Rad). The membranes were blocked with 5% nonfat dry milk in Tris-buffered saline containing 0.1% Tween 20, and incubated with specific antibodies against TLR4 (1:200), MMP-9 (1:400), PPARg (1:400), PPARa (1:100), IP-10 (1:5000), PKC (1:400), NF-kB (1:400) and b-actin (1:400).…”

Section: Western Blottingmentioning

confidence: 99%

PPARγ agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway

Liu

Wang

et al. 2009

Laboratory Investigation

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Atherosclerosis is increasingly recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, so as to promote the pathogenesis of atherosclerosis. Toll-like receptor 4 (TLR4) activates signaling pathways leading to the expression of pro-inflammatory cytokines implicated in the etiology of atherosclerosis. Peroxisome proliferator-activated receptor g (PPARg) agonists are considered to be important in modulating vascular inflammation and atherosclerosis. Herein, we investigated the modulatory effects of rosiglitazone on Ang II-mediated inflammatory responses both in vivo and in vitro. We also examined whether TLR4-dependent signaling pathway was involved in the inhibitory effects of rosiglitazone on Ang II-induced pro-inflammatory responses in vascular smooth muscle cells (VSMCs). Male Sprague-Dawley rats received Ang II by subcutaneous infusion and/or rosiglitazone per os for 7 days. Systolic blood pressure rise in Ang II-infused rats was attenuated by rosiglitazone. Rosiglitazone also reduced Ang II-induced generation of pro-inflammatory mediators (TLR4, matrix metalloproteinase-9 and tumor necrosis factor-a), but enhanced production of anti-inflammatory mediators (PPARg and 6-keto-PGF 1a ) both in vivo and in vitro. Furthermore, treatment of VSMCs with both the TLR4 inhibitor and TLR4 small-interfering RNA (siRNA) showed that the modulatory effects of rosiglitazone on Ang II-mediated inflammatory responses in VSMCs were related to TLR4. Treatment of the cells with rosiglitazone had little effect on Ang II receptors expression (AT1 and AT2), but downregulated AT1-dependent ERK1/2 activation. Then, treatment of VSMCs with TLR4 siRNA, interferon-gamma-inducible protein 10 (IP-10) siRNA and with the special protein kinase C (PKC) inhibitor further revealed that the signaling pathway (TLR4/IP-10/PKC/NF-kB) was involved in the inhibitory effects of rosiglitazone on Ang II-induced pro-inflammatory responses in VSMCs. In conclusion, TLR4 may be a drug target involved in the ameliorative effects of PPARg agonist, rosiglitazone, on Ang II-mediated inflammatory responses in VSMCs. Moreover, rosiglitazone exerts its anti-inflammatory effect by interfering with the TLR4-dependent signaling pathway (ERK1/2/TLR4/IP-10/PKC/NF-kB) to prevent and treat atherosclerotic diseases.

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Rosiglitazone inhibits angiotensin II-induced CTGF expression in vascular smooth muscle cells––Role of PPAR-γ in vascular fibrosis

Cited by 50 publications

References 52 publications

The PPARγ Agonist Protects Cardiomyocytes from Oxidative Stress and ApoptosisviaThioredoxin Overexpression

The PPARγ Agonist Protects Cardiomyocytes from Oxidative Stress and ApoptosisviaThioredoxin Overexpression

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

PPARγ agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway

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