A potential role of the renin-angiotensin-aldosterone system in epithelial-to-mesenchymal transition-induced renal abnormalities: Mechanisms and therapeutic implications

Balakumar, Pitchai; Sambathkumar, R; Mahadevan, Nanjaian; Muhsinah, Abdullatif Bin; Alsayari, Abdulrhman; Venkateswaramurthy, N.; Jagadeesh, Gowraganahalli

doi:10.1016/j.phrs.2019.104314

Cited by 36 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipid metabolism as well as glucose anabolism and catabolism are dramatically subject to certain environmental and genetic influences, which may alter their equilibrium, leading to metabolic or fibrotic disorders. To corroborate these observations, various widespread diseases associated with the onset of fibrosis, including IPF, cirrhosis, hepatitis, non-alcoholic steatohepatitis, chronic kidney disease, myocardial infarction, heart failure, diabetes and scleroderma, share common metabolic pathways [ 49 , 57 , 94 , 95 , 96 ]. The liver and lung are reported to share many immune/inflammatory responses to damage through the lung–liver axis.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, COX-derived prostanoids appear to play an important role in Toll-like receptor response [ 56 ]. Curiously, high glucose in cell cultures induces an increase in angiotensinogen, angiotensin-converting enzyme (ACE) and AT1R mRNA levels, as well as Ang II and TGF-β1 concentrations, promoting the epithelial–mesenchymal transition and fibronectin synthesis [ 57 ]. Aldosterone is also reported to impair metabolism and to stimulate the differentiation of 3T3-L1 cells and brown preadipocytes into mature adipocytes, influencing the expression of the adipokine gene [ 58 ].…”

Section: Metabolic Alterations In Ipfmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis

Bargagli

Refini

d’Alessandro

et al. 2020

IJMS

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder limited to the lung. New findings, starting from our proteomics studies on IPF, suggest that systemic involvement with altered molecular mechanisms and metabolic disorder is an underlying cause of fibrosis. The role of metabolic dysregulation in the pathogenesis of IPF has not been extensively studied, despite a recent surge of interest. In particular, our studies on bronchoalveolar lavage fluid have shown that the renin–angiotensin–aldosterone system (RAAS), the hypoxia/oxidative stress response, and changes in iron and lipid metabolism are involved in onset of IPF. These processes appear to interact in an intricate manner and to be related to different fibrosing pathologies not directly linked to the lung environment. The disordered metabolism of carbohydrates, lipids, proteins and hormones has been documented in lung, liver, and kidney fibrosis. Correcting these metabolic alterations may offer a new strategy for treating fibrosis. This paper focuses on the role of metabolic dysregulation in the pathogenesis of IPF and is a continuation of our previous studies, investigating metabolic dysregulation as a new target for fibrosis therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Metabolic Alterations In Ipfmentioning

confidence: 99%

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis

Bargagli

Refini

d’Alessandro

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Angiotensin II is a vasoactive peptide of the RAAS, which can activate interstitial fibroblasts and tubular cells, ultimately resulting in the development of fibrosis in patients with CKD (Balakumar et al, 2019). It has been largely demonstrated that TGF-beta serves as a key downstream mediator in Ang II-induced chronic renal fibrosis (Iekushi et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin II (Ang II) plays a critical role in hypertension-induced fibrogenic mechanisms. It is the main effector of the renin angiotensin aldosterone system (RAAS), and increasing its levels can promote RAAS activity, resulting in severe vascular, glomerular, and tubulointerstitial injuries along with the release of the cytokine TGF-beta through the angiotensin type 1 receptor (Balakumar et al, 2019). TGFbeta is required for Ang II to activate fibroblasts and induce fibrosis (Ehanire et al, 2015b;Angelov et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

163

130

View full text Add to dashboard Cite

Fibrosis is a common phenotype that often leads to the progression of blood pressure-induced chronic kidney disease (CKD). TGF-beta plays an important role in promoting pathogenesis, and NLRP3 is a critical mediator in the progression of blood pressure-induced CKD. However, the pathophysiological roles of the TGF-betamediated NLRP3 pathway in modulating fibrosis in blood pressure-induced CKD have not been elucidated. The present study aims to investigate the contribution of TGFbeta-mediated NLRP3 inflammasome to renal fibrosis in rats with high blood pressure. By treating rats with angiotensin II (Ang II) for 14 days, we observed the development of fibrosis, characterized by epithelial-mesenchymal transition (EMT) markers [alphasmooth muscle actin (alpha-SMA), MMP-2, and MMP-9]. Immunohistochemical analysis further revealed that TGF-beta and NLRP3 inflammasome activation [high-mobility group box 1 (HMGB1), IL-1beta, and NLRP3] were significantly upregulated in the kidney of rats with Ang II-induced hypertension. Interestingly, we observed that Ang II could not increase the production of NLRP3 proteins, but TGF-beta could induce NLRP3 protein expression in cultured NRK-52E cells. Furthermore, we speculated that TGF-beta played a pathogenic role in Ang II-induced CKD because TGF-beta induced the activation of NLRP3 inflammasomes and Gasdermin D cleavage expression. We also proved that the pharmacological inhibition of NLRP3 by ISO caused a decrease in TGF-beta-induced NLRP3 inflammasome activation and the expression of EMT markers (alpha-SMA and CollagenI) and Gasdermin D cleavage. Collectively, these results suggest that TGF-beta-mediated NLRP3 inflammasome activation may cause the release of HMGB1 and an increase in Gasdermin D cleavage in NRK-52E, thereby contributing to renal fibrosis in Ang II-induced CKD. These findings provide novel insights into the pathogenic role of NLRP3 in CKD associated with high blood pressure.

show abstract

“…It is established that the EMT process in cancer cells is associated with poor patient survival. Mechanism data indicated that the EMT is a key step in the progression of cancer and participates in metastasis 55 . During the EMT process, the adhesion feature of cancer cells is decreased (e.g., E-cadherin loss).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

et al. 2019

View full text Add to dashboard Cite

Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial-mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

show abstract

A potential role of the renin-angiotensin-aldosterone system in epithelial-to-mesenchymal transition-induced renal abnormalities: Mechanisms and therapeutic implications

Cited by 36 publications

References 53 publications

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

Contact Info

Product

Resources

About