Activation of peroxisome proliferator-activated receptor-γ by curcumin blocks the signaling pathways for PDGF and EGF in hepatic stellate cells

Lin, Jianguo; Chen, Anping

doi:10.1038/labinvest.2008.20

Cited by 81 publications

(57 citation statements)

References 50 publications

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“…It is known that there is an increase in cell proliferation, ECM production and α-SMA synthesis in activated HSCs compared with quiescent HSCs [26]. In our study, Sal B treatment caused the suppression of activated HSCs including the reduction of cell growth rate, type I collagen and α-SMA.…”

Section: Discussionsupporting

confidence: 52%

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

Guo

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear. Methods: Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined. Results: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p. Conclusion: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.

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Section: Discussionsupporting

confidence: 52%

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

Guo

Chen

et al. 2017

Cell Physiol Biochem

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“…TGF-b1 can also stimulate fibroblast proliferation and we demonstrated that curcumin can inhibit this in vitro proliferative response in a dose-and time-dependent manner as well. The concentration range of curcumin (10 -30 mM) used in previous studies was similar to that used in the present study (22). TGF-b1 mediates its biological effects through downstream signaling effectors that belong to the Smads protein family (23).…”

Section: Discussionmentioning

confidence: 65%

Curcumin Ameliorates Renal Fibrosis by Inhibiting Local Fibroblast Proliferation and Extracellular Matrix Deposition

Zhou¹,

Zhang²,

Xu³

et al. 2014

J Pharmacol Sci

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Abstract. Renal fibrosis is mainly characterized by activation and proliferation of interstitial fibroblasts and by excessive synthesis and accumulation of extracellular matrix (ECM) components, including fibronectin (FN) and collagen. This study investigated the effects of curcumin on proliferation of renal interstitial fibroblasts and their underlying mechanisms in vivo and in vitro. ECM components were visualized by Sirius red and immunohistochemistry staining and quantified by western blot analysis in mice with unilateral ureteral obstruction (UUO). Duplex staining for proliferating cell nuclear antigen and a-smooth muscle actin (a-SMA), as well as MTT and flow cytometry assays, were performed to measure fibroblast proliferation. Protein expression of phosphorylated Smad2/3 (p-Smad2/3) and peroxisome proliferator-activated receptor-g (PPAR-g) were assessed by western blotting. Curcumin treatment decreased the accumulation of type I collagen and FN in the kidney of animals with UUO. Activation of rat renal interstitial fibroblasts (NRK-49F) was induced by TGF-b1. Curcumin treatment inhibited fibroblast proliferation and the cell cycle was arrested in the G1 phase. Curcumin treatment upregulated the expression of PPAR-g and downregulated the expression of p-Smad2/3. These results suggest that curcumin treatment ameliorates renal fibrosis by reducing fibroblast proliferation and ECM accumulation mediated by PPAR-g and Smad-dependent TGF-b1 signaling.

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“…32 In particular, curcumin has been shown to induce expression of the transcription factor PPAR-g, leading to inhibition of mitogen-stimulated proliferation of HSCs. 33 In addition, curcumin blocked the activation of critical pro-fibrogenic pathways in rodent HSCs, including the activation of NF-kB and extracellular signalregulated kinase, propagation of signal transduction downstream of TGF-b receptors, and expression and signaling of PDGF-b receptor and EGF receptor. [33][34][35] These data indicate that curcumin may be a general inhibitor of fibrogenesis independent of the setting in which it develops.…”

Section: Discussionmentioning

confidence: 98%

“…33 In addition, curcumin blocked the activation of critical pro-fibrogenic pathways in rodent HSCs, including the activation of NF-kB and extracellular signalregulated kinase, propagation of signal transduction downstream of TGF-b receptors, and expression and signaling of PDGF-b receptor and EGF receptor. [33][34][35] These data indicate that curcumin may be a general inhibitor of fibrogenesis independent of the setting in which it develops. In this study, a direct effect on HSCs is suggested by the fact that expression of a-smooth muscle actin, a classical marker of fibrogenic cells derived from the activation of HSCs, was significantly reduced in mice receiving curcumin, and was associated with reduced expression of type I procollagen.…”

Section: Discussionmentioning

confidence: 98%

Curcumin limits the fibrogenic evolution of experimental steatohepatitis

Vizzutti

Provenzano

Galastri

et al. 2010

Laboratory Investigation

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Nonalcoholic steatohepatitis is characterized by the association of steatosis with hepatic cell injury, lobular inflammation and fibrosis. Curcumin is known for its antioxidant, anti-inflammatory and antifibrotic properties. The aim of this study was to test whether the administration of curcumin limits fibrogenic evolution in a murine model of nonalcoholic steatohepatitis. Male C57BL/6 mice were divided into four groups and fed a diet deficient in methionine and choline (MCD) or the same diet supplemented with methionine and choline for as long as 10 weeks. Curcumin (25 mg per mouse) or its vehicle (DMSO) was administered intraperitoneally every other day. Fibrosis was assessed by Sirius red staining and histomorphometry. Intrahepatic gene expression was measured by quantitative PCR. Hepatic oxidative stress was evaluated by staining for 8-OH deoxyguanosine. Myofibroblastic hepatic stellate cells (HSCs) were isolated from normal human liver tissue. The increase in serum ALT caused by the MCD diet was significantly reduced by curcumin after 4 weeks. Administration of the MCD diet was associated with histological steatosis and necro-inflammation, and this latter was significantly reduced in mice receiving curcumin. Curcumin also inhibited the generation of hepatic oxidative stress. Fibrosis was evident after 8 or 10 weeks of MCD diet and was also significantly reduced by curcumin. Curcumin decreased the intrahepatic gene expression of monocyte chemoattractant protein-1, CD11b, procollagen type I and tissue inhibitor of metalloprotease (TIMP)-1, together with protein levels of a-smooth muscle-actin, a marker of fibrogenic cells. In addition, curcumin reduced the generation of reactive oxygen species in cultured HSCs and inhibited the secretion of TIMP-1 both in basal conditions and after the induction of oxidative stress. In conclusion, curcumin administration effectively limits the development and progression of fibrosis in mice with experimental steatohepatitis, and reduces TIMP-1 secretion and oxidative stress in cultured stellate cells.

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Activation of peroxisome proliferator-activated receptor-γ by curcumin blocks the signaling pathways for PDGF and EGF in hepatic stellate cells

Cited by 81 publications

References 50 publications

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

Curcumin Ameliorates Renal Fibrosis by Inhibiting Local Fibroblast Proliferation and Extracellular Matrix Deposition

Curcumin limits the fibrogenic evolution of experimental steatohepatitis

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