Protective or deleterious role of Wnt/beta-catenin signaling in diabetic nephropathy: An unresolved issue

Guo, Qi; Zhong, Wei; Duan, Aosong; Sun, Guanggong; Cui, Wenpeng; Zhuang, Xiaohua; Liu, Lihua

doi:10.1016/j.phrs.2019.03.022

Cited by 34 publications

(26 citation statements)

References 71 publications

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“…Such findings also supported by other studies which have been conducted in alloxan, STZ, and db/db diabetic animal models which were attributed to the inhibitory effect of Salidroside on hepatic gluconeogenesis and its stimulatory effect on peripheral in STZ-+ uninephrectomy and HDF + STZ animal models. 20,32 Also, Salidroside is a well-known antioxidant that protected many organs against oxidative damage by scavenging ROS and upregulation of antioxidant enzymes. 20,21 The emerging role of the Wnt/β-catenin signalling pathway in the initiation and progression of DN in both T1DM and T2DM is well established.…”

Section: Discussionmentioning

confidence: 99%

“…20,32 Also, Salidroside is a well-known antioxidant that protected many organs against oxidative damage by scavenging ROS and upregulation of antioxidant enzymes. 20,21 The emerging role of the Wnt/β-catenin signalling pathway in the initiation and progression of DN in both T1DM and T2DM is well established. 15 Within this view, it was shown that higher levels of numerous Wnt proteins and subsequently activated β-catenin signalling occurs, nearly, in most renal cells of the diabetic kidney including the podocytes, mesangial cells, and tubular cells.…”

Section: Discussionmentioning

confidence: 99%

“…15 Within this view, it was shown that higher levels of numerous Wnt proteins and subsequently activated β-catenin signalling occurs, nearly, in most renal cells of the diabetic kidney including the podocytes, mesangial cells, and tubular cells. 12,20 In such a case, the active Wnt/β-catenin signalling pathway is associated Some glomerular space was diminished in some of the glomeruli (arrowhead). E and F, were taken from T1DM + Salidroside-treated rats and showed almost normal architectures as those observed in control rats with the presence of very little damage in proximal and convoluted tubules and absence of glomerular congestion.…”

Section: Discussionmentioning

confidence: 99%

“…Salidroside protected against DN by inhibiting the apoptosis of proximal renal tubular cells through inhibition of BIM. 20 Also, Salidroside inhibited the high glucose-induced proliferation of mesangial cells by suppressing the production of TGF-β1 and ERK1/2 signalling. 21 Interestingly, and independent of its hypoglycaemic effect, Salidroside prevented renal damage and reduces kidney fibrosis and glomerulosclerosis in Adriamycintreated mice by suppressing β-catenin signalling.…”

mentioning

confidence: 97%

“…14 Also inhibiting Wnt/β-catenin signalling using specific antibodies, Wnt inhibitors (DKK1, Klotho), ACE inhibitors, β-catenin inhibitors, or other drugs ameliorated kidney damage, renal inflammation and reduced the associated proteinuria and fibrosis in a variety of diabetic animals. [16][17][18][19][20] Hence, it is reasonable that any drug which can reduce blood glucose levels or inhibit Wnt/β-catenin signalling protects against DN. Salidroside is a major glycoside isolated from Rhodiola rosea (R. rosea L).…”

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confidence: 99%

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Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

Shati

Alfaifi

2020

Clin Exp Pharma Physio

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This study evaluated if the nephroprotective effect of Salidroside in type 1 diabetes mellitus (T1DM) involves modulation of Wnt/β‐catenin signalling pathways. Control or Streptozotocin (STZ, 50 mg/kg, iv)‐induced T1DM adult male Wister rats were treated with the vehicle and Salidroside (100 mg/kg, orally) for 8 weeks daily. As compared to T1DM‐induced rats, Salidroside improved kidney structure, reduced urinary protein and albumin level, increased creatinine clearance, and suppressed renal fibrosis. It also decreased mRNA and protein levels of Wnt1, Wnt3, and TGF‐β1, phosphorylation of Smad‐3, total and nuclear levels of β‐catenin, and levels and activities of cleaved caspase‐3. Concomitantly, Salidroside significantly increased the levels of p‐β‐catenin (Ser33/37/Thr41) and suppressed protein levels of Axin‐2, fibronectin, and, mRNA and protein levels of collagen IIIa, the main targets of β‐catenin. In both control and T1DM rats, Salidroside significantly lowered fasting glucose levels and reduced renal levels of reactive oxygen species (ROS) p‐and GS3Kβ (Ser9) but significantly increased levels of SOD and GSH. In conclusion, Salidroside protected the kidney of rats against T1DM‐induced injury and fibrosis by activating GS3Kβ‐induced inhibition of Wnt1/Wnt3a β‐catenin. This was associated with hypoglycaemic and antioxidant effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

See 3 more Smart Citations

Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

Shati

Alfaifi

2020

Clin Exp Pharma Physio

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Molecular mechanisms of diabetic nephropathy: A narrative review

Sun,

Guo,

et al. 2024

Cell Biology International

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Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end‐stage renal disease. It is attracting significant attention in both domestic and international research due to its widespread occurrence, fast advancement, and limited choices for prevention and treatment. The pathophysiology of this condition is intricate and involves multiple molecular and cellular pathways at various levels. This article provides a concise overview of the molecular processes involved in the development of DN. It discusses various factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, cellular damage, autophagy, and epigenetics. The aim is to offer clinicians a valuable reference for DN's diagnosis, treatment, and intervention.

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XAV‐939 inhibits epithelial‐mesenchymal transformation in pulmonary fibrosis induced by crystalline silica via the Wnt signaling pathway

et al. 2022

Environmental Toxicology

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Silicosis is an occupational lung disease that results from long-term inhalation of free silica dust, the expression is sustained inflammation response, fibroblast hyperplasia, and excessive collagen deposit, bringing about pulmonary interstitial fibrosis. Wnt signaling pathway exists in various kinds of eukaryotic cells, is a highly conservative signaling pathway in biological evolution, and participates in cell proliferation, differentiation, migration, and polarity of physiological activity, such as in embryonic development, organ morphology, and tumor. In addition, it plays an important role in the progress of fibrosis disease. At present, studies related to silicosis are increasing, but the pathogenesis of silicosis still is not clear. In recent years, more and more studies have suggested that the Wnt signaling pathway could participate in the pathogenesis of silicosis fibrosis. In the study, we explored the mechanism of the Wnt signaling pathway in the pathogenesis of silicosis fibrosis and evaluated the effect of XAV-939 treatment epithelial-mesenchymal transformation (EMT) induced by silica. In addition, the results showed that EMT and activation of the Wnt signaling pathway would occur after stimulation of silica or TGF-β1. However, after treatment with the Wnt signaling pathway inhibitor XAV-939, EMT was reversed and the expression of the β-catenin decreased. These results suggested that the Wnt signaling pathway is associated with EMT induced by silica and it could be a potential target for the treatment of silicosis.

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Protective or deleterious role of Wnt/beta-catenin signaling in diabetic nephropathy: An unresolved issue

Cited by 34 publications

References 71 publications

Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

Molecular mechanisms of diabetic nephropathy: A narrative review

XAV‐939 inhibits epithelial‐mesenchymal transformation in pulmonary fibrosis induced by crystalline silica via the Wnt signaling pathway

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