Emodin attenuates high glucose-induced TGF-β1 and fibronectin expression in mesangial cells through inhibition of NF-κB pathway

Yang, Jie; Zeng, Zhi; Wang, Teng; Yang, Zhicheng; Liu, Bing; Lan, Tian

doi:10.1016/j.yexcr.2013.10.006

Cited by 42 publications

(26 citation statements)

References 29 publications

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“…Emodin is an active constituent in rhubarb, one of the herbs in TSF. Emodin has been found to stabilize I κ B α to arrest p65 nuclear translocation and inhibit the DNA-binding and transcriptional activities of NF- κ B, thus suppressing high glucose-induced TGF- β 1 overexpression in mesangial cells [30]. Another herb in TSF is astragalus, whose active constituent is astragaloside IV, which has been shown to inhibit NF- κ B overexpression in the kidney of streptozotocin-induced diabetic rats [31].…”

Section: Discussionmentioning

confidence: 99%

Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats

Chen

Zhao

Zhang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Aim. This study investigated the effect and mechanism of the Chinese herbal medicine Tangshen Formula (TSF) on GI structure remodeling in the rat model of diabetes. Methods. Type 2 diabetic rats were used. Wet weight per unit length, layer thicknesses, levels of collagens I and III, nuclear factor kappa B (NF-κB), interferon-γ (IFN-γ), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and Smad2/3 expression in the rat colon were measured. Results. Compared with the control group animals, wet weight and layer thicknesses of the colon increased, and expressions of collagens I and III, NF-κB, IFN-γ, IL-6, TGF-β1, and Smad2/3 increased significantly in the diabetic animals. TSF inhibited increase in colonic wet weight and layer thicknesses, downregulated expressions of collagens I and III in the mucosal layer, and downregulated expressions of NF-κB, IFN-γ, IL-6, TGF-β1, and Smad2/3 in the colon wall. Furthermore, level of expression of NF-κB was associated with those of TGF-β1 and Smad2/3. Expression of TGF-β1 was associated with the most histomorphometric parameters including colonic weight, mucosal and muscle thicknesses, and levels of collagens I and III in mucosal layer. Conclusion. TSF appears to attenuate colonic structure remodeling in type 2 diabetic rats through inhibiting the overactivated pathway of NF-κB, thus reducing expressions of TGF-β1.

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Section: Discussionmentioning

confidence: 99%

Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats

Chen

Zhao

Zhang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…25,26,75,76,80,81 At the same time, it has been reported that NF-kB activation induces TGF-b production. [82][83][84] Thus, there is a potential positive feedback mechanism between TGF-b production and NF-kB activation that enhances the fibrotic process. (vi) Furthermore, we used RT-qPCR and protein detection by western blot to demonstrate that H 2 O 2 induces the expression and secretion of TGF-b1 and TGF-b2, and it has been clearly demonstrated that TGF-b1 and TGF-b2 induce the conversion of ECs into myofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

119

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During the pathogenesis of systemic inflammation, reactive oxygen species (ROS) circulate in the bloodstream and interact with endothelial cells (ECs), increasing intracellular oxidative stress. Although endothelial dysfunction is crucial in the pathogenesis of systemic inflammation, little is known about the effects of oxidative stress on endothelial dysfunction. Oxidative stress induces several functions, including cellular transformation. A singular process of cell conversion is tendothelial-to-mesenchymal transition, in which ECs become myofibroblasts, thus losing their endothelial properties and gaining fibrotic behavior. However, the participation of oxidative stress as an inductor of conversion of ECs into myofibroblasts is not known. Thus, we studied the role played by oxidative stress in this conversion and investigated the underlying mechanism. Our results show that oxidative stress induces conversion of ECs into myofibroblasts through decreasing the levels of endothelial markers and increasing those of fibrotic and ECM proteins. The underlying mechanism depends on the ALK5/Smad3/NF-kB pathway. Oxidative stress induces the expression and secretion of TGF-b1 and TGF-b2 and p38 MAPK phosphorylation. Downregulation of TGF-b1 and TGF-b2 by siRNA technology abolished the H 2 O 2 -induced conversion. To our knowledge, this is the first report showing that oxidative stress is able to induce conversion of ECs into myofibroblasts via TGF-b secretion, emerging as a source for oxidative stress-based vascular dysfunction. Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs into myofibroblasts through a TGF-b-dependent mechanism, changing the ECs protein expression profile, and converting normal ECs into pathological ones. This information will be useful in designing new and improved therapeutic strategies against oxidative stress-mediated systemic inflammatory diseases.

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“…EMO was shown to have antiinflammatory effects [38] and EMO also attenuated glucose-induced matrix synthesis in human peritoneal mesothelial cells [39]. Recent study have demonstrated that EMO reduced TGF-β1 and FN overexpression by inhibition of NF-κB activation, suggesting that EMO-mediated suppression of the NF-κB pathway could protect against DKD [40]. However, the effects of EMO on podocytes EMT in rats with DKD have not been investigated yet.…”

Section: Discussionmentioning

confidence: 99%

Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

Tingfang

Zheng

Xiao

et al. 2015

Cell Physiol Biochem

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Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg^-1· d^-1 and QLT0267 at 10 mg· kg^-1· w^-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.

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Emodin attenuates high glucose-induced TGF-β1 and fibronectin expression in mesangial cells through inhibition of NF-κB pathway

Cited by 42 publications

References 29 publications

Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats

Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

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