Qingshen Buyang Formula Attenuates Renal Fibrosis in 5/6 Nephrectomized Rats via Inhibiting EMT and Wnt/<i>β</i>-Catenin Pathway

Zhang, Xueqin; Fang, Jing; Chen, Zhiqiang; Zhao, Bingwu; Wu, Size; Yong-mei, Pan

doi:10.1155/2019/5370847

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…Frz can act on dishevelled protein (Dsh/Dvl), leading to β-catenin dissociation from the degradation complex, cytosolic accumulation and translocation into the nucleus, where it activates downstream targets such as fibrosis-associated molecules, including fibronectin (FN), matrix metalloproteinase-7 (MMP-7), Twist, and Snail. Abnormal changes in the Wnt signalling pathway can cause many kidney diseases such as renal carcinoma, acute kidney injury, and renal fibrosis [4][5][6]. In the process of kidney injury, multiple factors cause epithelial cells to transform into fibroblasts or myofibroblasts, resulting in a loss of renal tubules and ECM deposition.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-27a targets Sfrp1 to induce renal fibrosis in diabetic nephropathy by activating Wnt/β-Catenin signalling

et al. 2020

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Diabetic nephropathy (DN) commonly causes end-stage renal disease (ESRD). Increasing evidence indicates that abnormal miRNA expression is tightly associated with chronic kidney disease (CKD). This work aimed to investigate whether miR-27a can promote the occurrence of renal fibrosis in DN by suppressing the expression of secreted frizzled-related protein 1 (Sfrp1) to activate Wnt/β-catenin signalling. Therefore, we assessed the expression levels of miR-27a, Sfrp1, Wnt signalling components, and extracellular matrix (ECM)-related molecules in vitro and in vivo. Sfrp1 was significantly down-regulated in a high-glucose environment, while miR-27a levels were markedly increased. A luciferase reporter assay confirmed that miR-27a down-regulated Sfrp1 by binding to the 3′ untranslated region directly. Further, NRK-52E cells under high-glucose conditions underwent transfection with miR-27a mimic or the corresponding negative control, miR-27a inhibitor or the corresponding negative control, si-Sfrp1, or combined miR-27a inhibitor and si-Sfrp1. Immunoblotting and immunofluorescence were performed to assess the relative expression levels of Wnt/β-catenin signalling and ECM components. The mRNA levels of Sfrp1, miR-27a, and ECM-related molecules were also detected by quantitative real-time PCR (qPCR). We found that miR-27a inhibitor inactivated Wnt/β-catenin signalling and reduced ECM deposition. Conversely, Wnt/β-catenin signalling was activated, while ECM deposition was increased after transfection with si-Sfrp1. Interestingly, miR-27a inhibitor attenuated the effects of si-Sfrp1. We concluded that miR-27a down-regulated Sfrp1 and activated Wnt/β-catenin signalling to promote renal fibrosis.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-27a targets Sfrp1 to induce renal fibrosis in diabetic nephropathy by activating Wnt/β-Catenin signalling

et al. 2020

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“…Qingshen Buyang Formula significantly reduces the expression of collagen I and fibronectin, the main components of ECM. Furthermore, by inhibiting EMT and Wnt/β-catenin signaling pathway, it improves renal injury and relieves renal fibrosis (Zhang et al, 2019). Zhen-Wu-tang alleviates adenine-induced chronic renal failure (CRF) by regulating the canonical Wnt4/ β-catenin signaling, associated with improvement of renal fibrosis because it suppresses the overexpression of collagen IV and fibronectin, two key components of fibrosis (La et al, 2018).…”

Section: Specific Inhibition Of Wnt/β-catenin Signaling By Natural Productsmentioning

confidence: 99%

Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis

Sun

Hua

et al. 2021

Front. Pharmacol.

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The Wnt/β-catenin signaling pathway plays important roles in embryonic development and tissue homeostasis. Wnt signaling is induced, and β-catenin is activated, associated with the development and progression of renal fibrosis. Wnt/β-catenin controls the expression of various downstream mediators such as snail1, twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1, transient receptor potential canonical 6, and renin-angiotensin system components in epithelial cells, fibroblast, and macrophages. In addition, Wnt/β-catenin is usually intertwined with other signaling pathways to promote renal interstitial fibrosis. Actually, given the crucial of Wnt/β-catenin signaling in renal fibrogenesis, blocking this signaling may benefit renal interstitial fibrosis. There are several antagonists of Wnt signaling that negatively control Wnt activation, and these include soluble Fzd-related proteins, the family of Dickkopf 1 proteins, Klotho and Wnt inhibitory factor-1. Furthermore, numerous emerging small-molecule β-catenin inhibitors cannot be ignored to prevent and treat renal fibrosis. Moreover, we reviewed the knowledge focusing on anti-fibrotic effects of natural products commonly used in kidney disease by inhibiting the Wnt/β-catenin signaling pathway. Therefore, in this review, we summarize recent advances in the regulation, downstream targets, role, and mechanisms of Wnt/β-catenin signaling in renal fibrosis pathogenesis. We also discuss the therapeutic potential of targeting this pathway to treat renal fibrosis; this may shed new insights into effective treatment strategies to prevent and treat renal fibrosis.

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“…40 Abnormal changes in Wnt/β-catenin signaling is involved in many kidney diseases, including renal fibrosis, acute kidney injury, and renal carcinoma. [41][42][43] Wnt/β-catenin signaling was shown to be activated by KIF23 in gastric cancer. 44 Here, we investigated whether the miR-17-5p/KIF23 axis is responsible for Wnt/β-catenin signaling in high glucose-treated HMCs.…”

Section: Inhibition Of Mir-17-5p Activates Wnt/β-catenin Signaling In Hmcs By Upregulating Kif23 Expressionmentioning

confidence: 99%

MiR‐17‐5p downregulation alleviates apoptosis and fibrosis in high glucose‐induced human mesangial cells through inactivation of Wnt/β‐catenin signaling by targeting KIF23

Chen

Cheng

et al. 2021

Environmental Toxicology

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Diabetic nephropathy (DN) remains the major cause of end-stage renal disease.MicroRNAs (miRNAs) have been reported to perform biological functions in many diseases. This investigation elucidated the biological role of miR-17-5p in DN. In this study, high glucose-cultured human mesangial cells (HMCs) were used as a cell model of DN. The miR-17-5p and KIF23 expression was measured by RT-qPCR. Cell apoptosis was detected by flow cytometry. The protein levels of apoptosis markers, fibrosis markers, and Wnt/β-catenin signaling-related genes were assessed using western blotting. The interaction of miR-17-5p with KIF23 was tested by a luciferase reporter assay. We found that miR-17-5p was upregulated in both DN patients and high glucose-treated HMCs. Silencing miR-17-5p attenuated the apoptosis and fibrosis in high glucose-treated HMCs. MiR-17-5p binds to KIF23 3 0 UTR and negatively regulates KIF23 expression. KIF23 knockdown could suppress the role of miR-17-5p inhibition in high glucose-treated HMCs. Additionally, inhibition of miR-17-5p activated Wnt/β-catenin signaling in HMCs through upregulating KIF23 expression. Suppression of Wnt/β-catenin signaling antagonized the effect of miR-17-5p in HMCs.In conclusion, miR-17-5p inhibition alleviates the apoptosis and fibrosis in high glucose-treated HMCs by targeting KIF23 activating Wnt/β-catenin signaling.

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Qingshen Buyang Formula Attenuates Renal Fibrosis in 5/6 Nephrectomized Rats via Inhibiting EMT and Wnt/β-Catenin Pathway

Cited by 5 publications

References 32 publications

MicroRNA-27a targets Sfrp1 to induce renal fibrosis in diabetic nephropathy by activating Wnt/β-Catenin signalling

MicroRNA-27a targets Sfrp1 to induce renal fibrosis in diabetic nephropathy by activating Wnt/β-Catenin signalling

Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis

MiR‐17‐5p downregulation alleviates apoptosis and fibrosis in high glucose‐induced human mesangial cells through inactivation of Wnt/β‐catenin signaling by targeting KIF23

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