Role of the Wnt/β-catenin signaling pathway in inducing apoptosis and renal fibrosis in 5/6-nephrectomized rats

Xin, Lin; Zha, Yan; Zeng, Xiangzhen; Dong, Rong; Wang, Qinghua; Wang, Dong‐Tao

doi:10.3892/mmr.2017.6461

Cited by 38 publications

(26 citation statements)

References 31 publications

(30 reference statements)

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“…Given the vital role of myofibroblast proliferation in resveratrol‐mediated anti‐fibrosis, we speculated that proliferation‐related pathways likely participate in fibrogenesis. Previous studies have revealed that the MAPK, PI3K/Akt, JAK2/STAT3, and Wnt/β‐catenin signalling pathways are involved in renal fibrosis (Ai et al, ; Gao et al, ; Lin et al, ; Wang, Wang, et al, ; Wang, Zhou, et al, ). In this study, the activities of MAPK (Figure a), PI3K/Akt (Figure b), JAK2/STAT3 (Figure c), and Wnt/β‐catenin (Figure d) in the UUO group were enhanced compared with those in the sham‐operated group, indicating that activated signal transduction was involved in the proliferation and transdifferentiation of myofibroblasts.…”

Section: Resultsmentioning

confidence: 99%

Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation‐related signalling pathways

Zhang

Shen

et al. 2019

British J Pharmacology

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Background and Purpose: Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. Previous studies have shown that resveratrol has anti-fibrotic activity, but its potential molecular mechanisms of action are not well understood. Experimental Approach: The anti-fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF-β1 in vitro. Gene and protein expression levels were analysed by PCR, Western blotting, and immunohistochemical staining. Key Results: Resveratrol inhibits the myofibroblastic phenotype and fibrosis formation in UUO kidneys by targeting fibroblast-myofibroblast differentiation (FMD) and epithelial-mesenchymal transition (EMT). The anti-fibrotic effects of resveratrol correlated with decreased proliferation of TECs in the interstitium and tubules, resulting in suppressed activity of the proliferation-related signalling pathways, including that of the MAPK, PI3K/Akt, Wnt/β-catenin, and JAK2/STAT3 pathways. Resveratrol treatment suppressed TGF-β1-induced FMD and the expression of the myofibroblastic phenotype in fibroblasts in vitro by antagonizing the activation of proliferation-related signalling. Similarly, TGF-β1-mediated overactivation of the proliferation-related signalling in TECs induced EMT, and the myofibroblastic phenotype was suppressed by resveratrol. The anti-fibrotic and anti-proliferative effects of resveratrol were associated with the inactivation of Smad2/3 signalling and resulted in a partial reversal of FMD and EMT and the inhibition of the myofibroblastic phenotype. Conclusions and Implications:Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in vivo and in vitro via proliferation-related pathways, making it a potential therapeutic agent for preventing renal fibrosis.

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Section: Resultsmentioning

confidence: 99%

Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation‐related signalling pathways

Zhang

Shen

et al. 2019

British J Pharmacology

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“…Two important features of CKD, inflammation and oxidative stress, can drive the progression of CKD and lead to cardiovascular and other body system complications [6,7]. Moreover, another key feature of CKD is renal fibrosis, which is the final pathological stage of all progressive renal diseases [8,9]. As a model of CKD, 5/6 nephrectomized (5/6Nx) rats have been frequently used as to study the progression of CKD [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats

et al. 2018

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Salvianolic acid A (SAA) is a minor phenolic carboxylic acid extracted from Salviae miltiorrhizae Bunge (Danshen). SAA exhibits a variety of pharmacological activities, such as antioxidative, anti-thrombotic, neuroprotective, and anti-fibrotic effects, as well as protection from myocardial ischemia and prevention of diabetes and other diseases. Furthermore, SAA has shown renal-protective effects in doxorubicin-induced nephropathy. However, there has been limited research regarding the effects of SAA and underlying mechanisms in chronic kidney disease (CKD). Here, we examined the effects and molecular mechanisms of SAA in an established animal model of 5/6 nephrectomized (5/6Nx) rats. The rats were injected with SAA (2.5, 5, and 10 mg/kg per day, intraperitoneally (ip)) for 28 days. SAA dose-dependently lowered the levels of urine protein, blood urea nitrogen, serum creatinine, plasma total cholesterol, and plasma triglycerides in 5/6Nx rats. Histological examination revealed that SAA dose-dependently attenuated renal pathological lesions, evidenced by reduced renal tubulointerstitial fibrosis by decreasing the expression levels of tumor growth factor-β1 and α-smooth muscle actin in 5/6Nx rats. Moreover, SAA dose-dependently inhibited the activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, subsequently attenuating the secretion of tumor necrosis factor-α and interleukin-1β and inhibiting the expression of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in kidneys of 5/6Nx rats. The above results were consistent with those obtained in lipopolysaccharide-induced HK-2 cells in vitro (a recognized in vitro inflammatory model). In conclusion, our results demonstrated that SAA effectively attenuates kidney injury in 5/6Nx rats. The therapeutic effects of SAA on kidney injury can be attributed to its anti-inflammatory activities through inhibition of the activation of the NF-κB and p38 MAPK signaling pathways.

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“…Cisternas et al discussed the pro-brotic effect of Wnt signaling in both skeletal muscle and kidney [33]. Mounting evidence established that the Wnt/β-catenin signaling pathway plays a crucial role in regulating the development and progression of renal brotic lesions following injury [34][35][36]. The Wnt/β-catenin signal is relatively silent in the kidneys of healthy adults and is activated once the kidneys are subjected to various kinds of damages [37].…”

Section: Discussionmentioning

confidence: 99%

Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

Cao

Zeng

et al. 2020

Preprint

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Abstract Background: Renal fibrosis is a common pathological feature of chronic kidney disease (CKD). Aging accelerates renal fibrosis and further aggravates the process of CKD. Corallodiscus flabellata B. L. Burtt (C. flabellata) is a commonly used botanical drug in the Chinese population. However, few studies have reported its physiological effects. This study aimed to explore the effect of C. flabellata extract on renal fibrosis in aging mice and identify potentially active compounds. Methods: Using Senescence-accelerated mouse-prone 8 (SAMP8) mice and β-galactosidase (β-gal)-induced normal rat kidney epithelial cells (NRK-52E cells) as a model, to explore the mechanism of C. flabellata extract on senescence-related renal fibrosis, and initially clarified the material basis of C. flabellata. Results: The C. flabellata extract reduced the senescence and fibrosis of the kidneys in SAMP8 mice by activating nuclear factor erythroid 2–related factor 2 (Nrf2) to balance oxidative stress and inflammation, and interrupting the fibrinogen signaling in the Wnt/β-catenin/renin–angiotensin system. Moreover, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated compounds from C. flabellata, which reduced the senescence of NRK-52E cells, and maybe the material basis for the function of C. flabellata. Conclusion: Our experiments illuminated that the extract of C. flabellata may improve the aging-related renal fibrosis through the Wnt/β-catenin/RAS pathway, and the material basis of its function may be SDC-0-14, 16 and SDC-1- 8.

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Role of the Wnt/β-catenin signaling pathway in inducing apoptosis and renal fibrosis in 5/6-nephrectomized rats

Cited by 38 publications

References 31 publications

Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation‐related signalling pathways

Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation‐related signalling pathways

Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats

Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

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