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Wnt/?-catenin regulates blood pressure and kidney injury in rats.

ABSTRACT: Activation of the renin-angiotensin system (RAS) plays a pivotal role in mediating hypertension, chronic kidney and cardiovascular diseases. As Wnt/?-catenin regulates multiple RAS genes, we speculated that this developmental signaling pathway might also participate in blood pressure (BP) regulation. To test this, we utilized two rat models of experimental hypertension: chronic angiotensin II infusion and remnant kidney after 5/6 nephrectomy. Inhibition of Wnt/?-catenin by ICG-001 blunted angiotensin II-induced hypertension. Interestingly, angiotensin II was able to induce the expression of multiple Wnt genes in vivo and in vitro, thereby creating a vicious cycle between Wnt/?-catenin and RAS activation. In the remnant kidney model, renal ?-catenin was upregulated, and delayed administration of ICG-001 also blunted BP elevation and abolished the induction of angiotensinogen, renin, angiotensin-converting enzyme and angiotensin II type 1 receptor. ICG-001 also reduced albuminuria, serum creatinine and blood urea nitrogen, and inhibited renal expression of fibronectin, collagen I and plasminogen activator inhibitor-1, and suppressed the infiltration of CD3+ T cells and CD68+ monocytes/macrophages. In vitro, incubation with losartan prevented Wnt/?-catenin-mediated fibronectin, ?-smooth muscle actin and Snail1 expression, suggesting that the fibrogenic action of Wnt/?-catenin is dependent on RAS activation. Taken together, these results suggest an intrinsic linkage of Wnt/?-catenin signaling with BP regulation. Our studies also demonstrate that hyperactive Wnt/?-catenin can drive hypertension and kidney damage via RAS activation.

SUBMITTER: Xiao L

PROVIDER: S-EPMC6502648 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Wnt/β-catenin regulates blood pressure and kidney injury in rats.

Xiao Liangxiang L Xu Bo B Zhou Lili L Tan Roderick J RJ Zhou Dong D Fu Haiyan H Li Aiqing A Hou Fan Fan FF Liu Youhua Y

Biochimica et biophysica acta. Molecular basis of disease 20190130 6

Activation of the renin-angiotensin system (RAS) plays a pivotal role in mediating hypertension, chronic kidney and cardiovascular diseases. As Wnt/β-catenin regulates multiple RAS genes, we speculated that this developmental signaling pathway might also participate in blood pressure (BP) regulation. To test this, we utilized two rat models of experimental hypertension: chronic angiotensin II infusion and remnant kidney after 5/6 nephrectomy. Inhibition of Wnt/β-catenin by ICG-001 blunted angiot ...[more]

PMID: 30710617

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Project description:ObjectiveTo investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid β- (Aβ-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/β-catenin pathway.MethodsHealthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/β-catenin pathway-related proteins, respectively.ResultsOn the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aβ-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/β-catenin pathway by upregulating Wnt3a, β-catenin, Disheveled (Dvl), and p-GSK3β and downregulating p-β-catenin and GSK3β.ConclusionLME attenuates cognitive impairment in Aβ-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/β-catenin pathway.

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Wnt/?-catenin regulates blood pressure and kidney injury in rats.

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Wnt/β-catenin regulates blood pressure and kidney injury in rats.

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