Podocyte Wnt/ß-catenin pathway is activated by integrin-linked kinase in clinical and experimental focal segmental glomerulosclerosis

Naves, Marcelo Andery; Requião-Moura, Lúcio R.; Soares, Maria Fernanda; Silva-Junior, Jose A.; Kirsztajn, Gianna Mastroianni; Teixeira, Vicente P.C.

doi:10.5301/jn.5000017

Cited by 24 publications

(16 citation statements)

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“…CaMK II/CREB signaling activation can regulate many downstream target genes expression, among which Wnt has gained our attention (51)(52)(53). Previous studies including ours show that Wnt/␤-catenin signaling activation could promote podocyte dedifferentiation and proteinuria (26,54,55). We have also reported that factors such as adriamycin and TGF␤1 could induce Wnt/␤-catenin signaling activation in podocytes.…”

Section: Discussionmentioning

confidence: 70%

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

Jiang

Song

et al. 2013

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 70%

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

Jiang

Song

et al. 2013

Journal of Biological Chemistry

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“…The continuous activation of the Wnt signaling pathway in renal podocytes was commonly involved in the development of proteinuria and glomerulosclerosis [5, 20]. Many recent studies have shown that the Wnt/ β -catenin signaling pathway was closely related to diabetic nephropathy [21, 22].…”

Section: Discussionmentioning

confidence: 99%

Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/β‐Catenin Signaling Pathway in Diabetic Rats

Bai

Huo

Chen

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH). Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured. At the end of the 20th week, biochemical parameters and body weight were tested. The kidney tissues were observed under light microscope and transmission electron microscopy. We examined Wnt/beta-catenin signaling pathway key proteins and renal interstitial fibrosis related molecular markers expression. The results showed that HTH could reduce urinary protein excretion and relieve renal pathological damage. Wnt4, p-GSK3β (S9), and β-catenin expression were decreased in the signaling pathway, but GSK3β level was not changed by HTH in diabetic rats. Furthermore, the expressions of TGF-β1 and ILK were decreased, but the level of E-cadherin was increased in diabetic rats after treatment with HTH. This study demonstrated that HTH could inhibit the high expression of Wnt/β-catenin pathway in kidney of diabetic rats. The effect might be one of the main ways to reduce urinary protein excretion.

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“…One upstream regulator of β-catenin is ILK, which is itself upregulated by a variety of injurious stimuli such as adriamycin, puromycin, high glucose levels, TGF-β1 and angiotensin II. 17,65 Although controversy exists as to whether ILK is a true kinase, 66,67 upregulation of ILK is reported to lead to GSK-3β phosphorylation and β-catenin stabilization in many cell types including podocytes. ILK is also upregulated in glomerular podocytes in mouse models and in biopsy samples from patients with proteinuric CKD, and its inhibitor ameliorates proteinuria in mice with adriamycin-induced injury.…”

Section: Wnt/β-catenin and Podocyte Dysfunctionmentioning

confidence: 99%

Wnt/β-catenin signalling and podocyte dysfunction in proteinuric kidney disease

2015

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Podocytes are unique, highly specialized, terminally differentiated cells that are integral components of the kidney glomerular filtration barrier. Podocytes are vulnerable to a variety of injuries and in response they undergo a series of changes ranging from hypertrophy, autophagy, dedifferentiation, mesenchymal transition and detachment to apoptosis, depending on the nature and extent of the insult. Emerging evidence indicates that Wnt/β-catenin signalling has a central role in mediating podocyte dysfunction and proteinuria. Wnts are induced and β-catenin is activated in podocytes in various proteinuric kidney diseases. Genetic or pharmacologic activation of β-catenin is sufficient to impair podocyte integrity and causes proteinuria in healthy mice, whereas podocyte-specific ablation of β-catenin protects against proteinuria after kidney injury. Mechanistically, Wnt/β-catenin controls the expression of several key mediators implicated in podocytopathies, including Snail1, the renin–angiotensin system and matrix metalloproteinase 7. Wnt/β-catenin also negatively regulates Wilms tumour protein, a crucial transcription factor that safeguards podocyte integrity. Targeted inhibition of Wnt/β-catenin signalling preserves podocyte integrity and ameliorates proteinuria in animal models. This Review highlights advances in our understanding of the pathomechanisms of Wnt/β-catenin signalling in mediating podocyte injury, and describes the therapeutic potential of targeting this pathway for the treatment of proteinuric kidney disease.

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Podocyte Wnt/ß-catenin pathway is activated by integrin-linked kinase in clinical and experimental focal segmental glomerulosclerosis

Abstract: Our findings suggest that activation of ILK activated the Wnt signaling pathway in damaged podocytes. This phenomenon could have an important role in development and/or progression of clinical and experimental FSGS.

Cited by 24 publications

References 0 publications

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/β‐Catenin Signaling Pathway in Diabetic Rats

Wnt/β-catenin signalling and podocyte dysfunction in proteinuric kidney disease

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