Aldosterone is involved in the pathogenesis of obesity-related glomerulopathy through activation of Wnt/β-catenin signaling in podocytes

Zhu, Jiajia; Chen, Yipu; Yang, Min; Liu, Bao-li; Dong, Jing; Dong, Hong-rui; Rui, Hongliang; Cheng, Hong

doi:10.3892/mmr.2018.8386

Cited by 18 publications

(29 citation statements)

References 42 publications

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“…Potential mechanisms for this reduction in body weight with SMC-specific MR deletion are unclear. While aldosterone and MR signaling have been implicated in the components of the metabolic syndrome associated with obesity ( 52 , 53 ), and MR blockade prevents obesity-induced metabolic syndrome in some animal models ( 54 , 55 ), this relationship has not held true in human studies ( 56 – 58 ). Further, to our knowledge, no data currently exists linking SMC-specific MR to the development of obesity and metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

No Significant Role for Smooth Muscle Cell Mineralocorticoid Receptors in Atherosclerosis in the Apolipoprotein-E Knockout Mouse Model

Moss

DuPont

Iyer

et al. 2018

Front. Cardiovasc. Med.

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Objective: Elevated levels of the hormone aldosterone are associated with increased risk of myocardial infarction and stroke in humans and increased progression and inflammation of atherosclerotic plaques in animal models. Aldosterone acts through the mineralocorticoid receptor (MR) which is expressed in vascular smooth muscle cells (SMCs) where it promotes SMC calcification and chemokine secretion in vitro. The objective of this study is to explore the role of the MR specifically in SMCs in the progression of atherosclerosis and the associated vascular inflammation in vivo in the apolipoprotein E knockout (ApoE−/−) mouse model.Methods and Results: Male ApoE−/− mice were bred with mice in which MR could be deleted specifically from SMCs by tamoxifen injection. The resulting atheroprone SMC-MR-KO mice were compared to their MR-Intact littermates after high fat diet (HFD) feeding for 8 or 16 weeks or normal diet for 12 months. Body weight, tail cuff blood pressure, heart and spleen weight, and serum levels of glucose, cholesterol, and aldosterone were measured for all mice at the end of the treatment period. Serial histologic sections of the aortic root were stained with Oil Red O to assess plaque size, lipid content, and necrotic core area; with PicroSirius Red for quantification of collagen content; by immunofluorescent staining with anti-Mac2/Galectin-3 and anti-smooth muscle α-actin antibodies to assess inflammation and SMC marker expression; and with Von Kossa stain to detect plaque calcification. In the 16-week HFD study, these analyses were also performed in sections from the brachiocephalic artery. Flow cytometry of cell suspensions derived from the aortic arch was also performed to quantify vascular inflammation after 8 and 16 weeks of HFD. Deletion of the MR specifically from SMCs did not significantly change plaque size, lipid content, necrotic core, collagen content, inflammatory staining, actin staining, or calcification, nor were there differences in the extent of vascular inflammation between MR-Intact and SMC-MR-KO mice in the three experiments.Conclusion: SMC-MR does not directly contribute to the formation, progression, or inflammation of atherosclerotic plaques in the ApoE−/− mouse model of atherosclerosis. This indicates that the MR in non-SMCs mediates the pro-atherogenic effects of MR activation.

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Section: Discussionmentioning

confidence: 99%

No Significant Role for Smooth Muscle Cell Mineralocorticoid Receptors in Atherosclerosis in the Apolipoprotein-E Knockout Mouse Model

Moss

DuPont

Iyer

et al. 2018

Front. Cardiovasc. Med.

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“…Third, Ang II binds to mineralocorticoid receptors directly, facilitating sodium and water reabsorption [28]. Furthermore, the increased aldosterone in the setting of obesity generates reactive oxygen species which injures podocytes and causes kidney dysfunction [29] (Fig. 1).…”

Section: Pathogenesis Of Orgmentioning

confidence: 99%

Obesity-Related Glomerulopathy: A Latent Change in Obesity Requiring More Attention

Yang

Cao

Deng

et al. 2020

Kidney Blood Press Res

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Background: Obesity has become a major public health problem, and the prevalence of kidney diseases has increased in parallel. Among kidney diseases caused by metabolic disorders, obesity-related glomerulopathy (ORG) is secondary to obesity. Summary: ORG is mainly caused by glomerular hyperfiltration, dysregulation of hormone and cytokine secretion in adipose tissues, and ectopic lipid accumulation in renal cells. ORG is pathologically characterized by glomerular hypertrophy, with or without focal and segmental glomerulosclerosis. Patients with ORG usually present with proteinuria concomitant with metabolic disorders such as dyslipidemia and hypertension. Weight loss, RAAS inhibitors, and improved insulin resistance can reduce the progression of ORG. Conclusion: ORG is a growing renal pathological change in obese individuals, and a comprehensive understanding of the disease is pivotal to avoid its occurrence and improve quality of life for those with obesity. Key Messages: This review comprehensively describes the characteristics of ORG in pathological changes, clinical manifestations, pathogeneses and treatments.

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“…In addition, similarly to the results in the PAH rat model, SP downregulated the expressions of AQP1 as well as β-catenin in PASMCs dealt with ALDO. Zhu et al [41] mentioned that ALDO was associated with obesityrelated glomerulopathy via β-catenin in podocytes. Thus, we speculated that when PAH was triggered, AQP1 and β-catenin act as 2 critical factors through which SP exerted its regulatory role.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone Contributed to Pulmonary Arterial Hypertension Development via Stimulating Aquaporin Expression and Pulmonary Arterial Smooth Muscle Cells Proliferation

Wang

Zhong

et al. 2020

Pharmacology

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Introduction and Objective: The regulatory network of aquaporin (AQP) 1 and renin-angiotensin-aldosterone (ALDO) system are not quite clear in pulmonary arterial hypertension (PAH). Thus, we explored the role of AQP1, ALDO and spirolactone (SP) in the PAH animal model and pulmonary arterial smooth muscle cells (PASMCs). Method: PAH rat model was established by monocrotaline (MCT) via intraperitoneal in SD rat. Hemodynamic measurement was conducted via the external jugular vein cannula. PASMCs were extracted from normal SD rat and cultured in SmGM medium. α-Actin expression was identified by immunocytochemistry. Protein levels were assessed by Western blot. Cell viability was assayed using the MTT method. Apoptosis rate was evaluated by flow cytometry. ALDO level was measured by ELISA. Result: SP decreased AQP1 and β-catenin expressions in PAH rat model induced successfully by MCT. Moreover, ALDO increased AQP1 expression and cell viability in PASMCs, which were extracted from rat and identified by α-actin expression. AQP1 downregulation decreased β-catenin expression, and SP lowered AQP1 and β-catenin expressions elevated by ALDO in PASMCs. SP offset ALDO's effect on the upregulation of cell viability as well as AQP1 and β-catenin expressions in PASMCs. In addition, AQP1 downregulation and SP have a negative effect on Ki-67 and proliferating cell nuclear antigen expressions as well as cell viability after ALDO treatment in PASMCs. Conclusion: ALDO might contribute to PAH development via stimulating AQP1 expression and PASMCs proliferation. However, SP could be considered an effective drug regulating PASMCs proliferation through modulating AQP1 and β-catenin expressions in PAH.

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Aldosterone is involved in the pathogenesis of obesity-related glomerulopathy through activation of Wnt/β-catenin signaling in podocytes

Cited by 18 publications

References 42 publications

No Significant Role for Smooth Muscle Cell Mineralocorticoid Receptors in Atherosclerosis in the Apolipoprotein-E Knockout Mouse Model

No Significant Role for Smooth Muscle Cell Mineralocorticoid Receptors in Atherosclerosis in the Apolipoprotein-E Knockout Mouse Model

Obesity-Related Glomerulopathy: A Latent Change in Obesity Requiring More Attention

Aldosterone Contributed to Pulmonary Arterial Hypertension Development via Stimulating Aquaporin Expression and Pulmonary Arterial Smooth Muscle Cells Proliferation

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