The aldosterone receptor antagonist spironolactone prevents peritoneal inflammation and fibrosis

Zhang, Lei; Hao, Jianbing; Ren, Liwei; Ding, Jianxun; Hao, Lirong

doi:10.1038/labinvest.2014.69

Cited by 30 publications

(29 citation statements)

References 41 publications

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“…Moreover, fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction (Divoux and Clement, 2011). Recent reports indicate that spironolactone limits peritoneal fibrosis in rats, opening up the possibility to improve the efficiency of peritoneal dialysis (Vazquez-Rangel et al, 2014;Yelken et al, 2014;Zhang et al, 2014). In addition, spironolactone may be beneficial for the cardiovascular function of these patients (Ito et al, 2014).…”

Section: Mineralocorticoid Receptor Activation Leads To Fibrosismentioning

confidence: 99%

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

2015

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Section: Mineralocorticoid Receptor Activation Leads To Fibrosismentioning

confidence: 99%

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

2015

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“…Studies illustrate activation of the renin-angiotensin-aldosterone system (RAAS) is a risk factor for the development of fibrosis [13,14]. Spironolactone is the most common aldosterone receptor antagonist used to pharmacologically block actions of aldosterone and for treatment of congestive heart failure, liver cirrhosis and hypertension.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Spironolactone on Endothelial-to-Mesenchymal Transition in HUVECs via Notch Pathway

Chen

Cai

Zhou

et al. 2015

Cell Physiol Biochem

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Background: Fibrosis results in excessive buildup of extracellular matrix proteins along with abnormalities in structure and is partly derived by a process involving transforming growth factor β (TGF-β) called endothelial-to-mesenchymal transition (EndMT). We investigated whether the aldosterone receptor-blocker spironolactone could abrogate TGF-β-induced fibrosis in EndMT and the underlying mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were divided into 5 groups for treatment: blank; vehicle control; TGF-β (10 ng/ml); spironolactone (1 μM)+TGF-β; and spironolactone+TGF-β+DAPT (10 μM). Cell chemotaxis was assayed by transwell assay. The expression of CD31 and vimentin was determined by Immunofluorescence staining and western blot analysis. Notch1 protein level was detected by western blot analysis. Results: Spironolactone significantly prevented TGF-β-stimulated EndMT by down-regulate vimentin and up-regulate CD31 in HUVECs (p<0.01).It inhibited cell migration during EndMT (p<0.01). The protective effect of spironolactone against EndMT could be attenuated by blocking the Notch signal pathway with DAPT (p<0.01). Notch signaling was activated and cross-interacted with TGF-β and spironolactone in regulating EndMT in HUVECs and reversed the spironolactone-related signaling by abrogating the antifibrotic actions with decreased Notch1 protein expression (p<0.01). Conclusion: Spironolactone may have a protective role in TGF-β-induced EndMT in HUVECs mediated by the Notch signal pathway.

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“…Treatment with spironolactone suppressed macrophage infiltration, neoangiogenesis, and fibrosis, which is associated with the suppression of TGF-β and PAI-1 expression, thereby resulting in improvement of peritoneal dysfunction, including ultrafiltration, glucose transport, and albumin leakage [38]. The effects of spironolactone have also been shown in the LPS-induced peritoneal injury model [36].…”

Section: Scraping Modelmentioning

confidence: 97%

“…We suggest that a model of peritoneal fibrosis induced in a peritonitis model will help identify new strategies for preventing peritoneal fibrosis. Many studies have used the LPS-induced peritoneal injury model [26][27][28][29][30][31][32][33][34][35][36]. LPS derived from Escherichia coli (Sigma, St. Louis, MO) is frequently used [26-30, 33, 35].…”

Section: Non-infectious Peritonitis Modelsmentioning

confidence: 99%

Peritonitis-induced peritoneal injury models for research in peritoneal dialysis review of infectious and non-infectious models

et al. 2017

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Peritonitis is an important complication of peritoneal dialysis. Several animal peritonitis models have been described, including bacterial and fungal models that are useful for studying inflammation in peritonitis. However, these models have limitations for investigating peritoneal fibrosis induced by acute inflammation and present difficulties in handling the infected animals. Animal models of peritonitis which induced peritoneal fibrosis are important for establishing new therapies to improve peritoneal damage induced by peritonitis. Here, we present an overview of representative animal models of peritoneal dialysis-associated infectious and non-infectious peritonitis, including our novel animal models (scraping and zymosan models) that mimic peritoneal injury associated with fibrosis and neoangiogenesis caused by bacterial or fungal peritonitis.

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The aldosterone receptor antagonist spironolactone prevents peritoneal inflammation and fibrosis

Cited by 30 publications

References 41 publications

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

Protective Effect of Spironolactone on Endothelial-to-Mesenchymal Transition in HUVECs via Notch Pathway

Peritonitis-induced peritoneal injury models for research in peritoneal dialysis review of infectious and non-infectious models

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