Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Guo, Zheng; Cai, Jiejie; Chen, Xingxing; Chen, Lingzhi; Ge, Wei; Zhou, Xi; Zhou, Hao

doi:10.1248/bpb.b16-00882

Cited by 13 publications

(6 citation statements)

References 27 publications

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“…Recent studies showed that serelaxin inhibits EndMT within the heart and kidney of isoprenaline-induced cardiomyopathy in rodents (Cai et al, 2017;Zheng et al, 2017). Zhou et al found that serelaxin improves cardiac function in rats with myocardial fibrosis, by reducing EndMT and interstitial collagens I and III, while increasing the microvascular density of the heart (Zhou et al, 2015).…”

Section: Relaxin Effects On Endothelial-to-mesenchymal Transitionmentioning

confidence: 99%

Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways

Shen

Samuel

et al. 2019

Molecular and Cellular Endocrinology

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Fibrosis is associated with accumulation of excess fibrillar collagen, leading to tissue dysfunction. Numerous processes, including inflammation, myofibroblast activation, and endothelial-tomesenchymal transition, play a role in the establishment and progression of fibrosis. Relaxin is a peptide hormone with well-known antifibrotic properties that result from its action on numerous cellular targets to reduce fibrosis. Relaxin activates multiple signal transduction pathways as a mechanism to suppress inflammation and myofibroblast activation in fibrosis. In this review, the general mechanisms underlying fibrotic diseases are described, along with the current state of knowledge regarding cellular targets of relaxin. Finally, an overview is presented summarizing the signaling pathways activated by relaxin and other relaxin family peptide receptor agonists to suppress fibrosis.

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Section: Relaxin Effects On Endothelial-to-mesenchymal Transitionmentioning

confidence: 99%

Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways

Shen

Samuel

et al. 2019

Molecular and Cellular Endocrinology

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“…A total of 40 signaling pathways were identified. In the most significantly altered signaling pathway in this study, fibrosis was reported in previous studies to be involved in the ‘Hedgehog signaling pathway’ ( 35 – 37 ), ‘ABC transporters’ ( 38 ), ‘ErbB signaling pathway’ ( 39 , 40 ), ‘cAMP signaling pathway’ ( 41 , 42 ), ‘Relaxin signaling pathway’ ( 43 , 44 ), ‘Ras signaling pathway’ ( 45 , 46 ) and ‘PI3K-Akt signaling pathway’ ( 47 , 48 ). Additionally, six ECM-associated pathways were directly associated with renal fibrosis.…”

Section: Discussionmentioning

confidence: 52%

Integrative microRNA and mRNA expression profiling in acute aristolochic acid nephropathy in mice

Zhu

Wang

et al. 2020

Mol Med Rep

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in acute aristolochic acid nephropathy (aan), aristolochic acid (aa) induces renal injury and tubulointerstitial fibrosis. However, the roles of micrornas (mirnas/mirs) and mrnas involved in aan are not clearly understood. The aim of the present study was to examine aa-induced genome-wide differentially expressed (de) mirnas and de mrnas using deep sequencing in mouse kidneys, and to analyze their regulatory networks. in the present self-controlled study, mice were treated with 5 mg/kg/day aa for 5 days, following unilateral nephrectomy. AA-induced renal injury and tubulointerstitial fibrosis were detected using hematoxylin and eosin staining and Masson's trichrome staining in the mouse kidneys. a total of 82 DE miRNAs and 4,605 DE mRNAs were identified between the aa-treated group and the self-control group. of these de mirnas and mrnas, some were validated using reverse transcription-quantitative Pcr. expression levels of the profibrotic miR-21, miR-433 and miR-132 families were significantly increased, whereas expression levels of the anti-fibrotic miR-122-5p and let-7a-1-3p were significantly decreased. Functions and signaling pathways associated with the de mirnas and mrnas were analyzed using Gene ontology and Kyoto encyclopedia of Genes and Genomes (KeGG). a total of 767 de pairs (in opposing directions) of mirnas and their mrna targets were identified. among these, regulatory networks of mirnas and mrnas were analyzed using KeGG to identify enriched signaling pathways and extracellular matrix-associated pathways. in conclusion, the present study identified genome-wide de mirnas and mrnas in the kidneys of aa-treated mice, as well as their regulatory pairs and signaling networks. The present results may improve the understanding of the role of de mirnas and their mrna targets in the pathophysiology of acute aan.

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“…4 week post-MI, animals presented renal fibrosis, oxidative stress and inflammation. We show for the first time that these alterations were Several studies have demonstrated that MI is associated with renal damage (24,25). ER is an organelle essential for protein biosynthesis and post-translational modifications, which is very sensitive to unfolded and misfolded proteins in the lumen of ER.…”

Section: Discussionmentioning

confidence: 65%

Role of endoplasmic reticulum stress in renal damage after myocardial infarction

et al. 2021

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Myocardial infarction (MI) is associated with renal alterations resulting in poor outcomes in patients with MI. Renal fibrosis is a potent predictor of progression in patients and is often accompanied by inflammation and oxidative stress; however, the mechanisms involved in these alterations are not well established. Endoplasmic reticulum (ER) plays a central role in protein processing and folding. An accumulation of unfolded proteins leads to ER dysfunction, termed ER stress. Since the kidney is the organ with highest protein synthesis fractional rate, we herein investigated the effects of MI on ER stress at renal level, as well as the possible role of ER stress on renal alterations after MI. Patients and MI male Wistar rats showed an increase in the kidney injury marker neutrophil gelatinase-associated lipocalin (NGAL) at circulating level or renal level respectively. Four weeks post-MI rats presented renal fibrosis, oxidative stress and inflammation accompanied by ER stress activation characterized by enhanced immunoglobin binding protein (BiP), protein disulfide-isomerase A6 (PDIA6) and activating transcription factor 6-alpha (ATF6α) protein levels. In renal fibroblasts, palmitic acid (PA; 50-200 µM) and angiotensin II (Ang II; 10−8 to 10−6M) promoted extracellular matrix, superoxide anion production and inflammatory markers up-regulation. The presence of the ER stress inhibitor, 4-phenylbutyric acid (4-PBA; 4 µM), was able to prevent all of these modifications in renal cells. Therefore, the data show that ER stress mediates the deleterious effects of PA and Ang II in renal cells and support the potential role of ER stress on renal alterations associated with MI.

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Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Cited by 13 publications

References 27 publications

Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways

Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways

Integrative microRNA and mRNA expression profiling in acute aristolochic acid nephropathy in mice

Role of endoplasmic reticulum stress in renal damage after myocardial infarction

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