Pretreatment with Relaxin Does Not Restore NO-Mediated Modulation of Calcium Signal in Coronary Endothelial Cells Isolated from Spontaneously Hypertensive Rats

Nistri, Silvia; Mannelli, Lorenzo Di Cesare; Ghelardini, Carla; Zanardelli, Matteo; Bani, Danièle; Failli, Paola

doi:10.3390/molecules20069524

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…These findings beg the question of how receptor expression changes over the course of disease. Restoration of calcium signalling via NO is impaired in the endothelium of spontaneously hypertensive rats and cannot be remediated by rhRLX, unlike that of Wistar Kyoto control rats (Nistri et al , ), suggesting differential responsiveness based on phenotype or pathological state. Indeed, as in the disease state, alterations in the ECM environment of cell culture matter, especially in the context of myofibroblasts.…”

Section: Anti‐fibrotic Effects Of Relaxin On the Integumentary Systemmentioning

confidence: 99%

Anti‐fibrotic actions of relaxin

Samuel

Royce

Hewitson

et al. 2016

British J Pharmacology

119

115

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Fibrosis refers to the hardening or scarring of tissues that usually results from aberrant wound healing in response to organ injury, and its manifestations in various organs have collectively been estimated to contribute to around 45-50% of deaths in the Western world. Despite this, there is currently no effective cure for the tissue structural and functional damage induced by fibrosisrelated disorders. Relaxin meets several criteria of an effective anti-fibrotic based on its specific ability to inhibit pro-fibrotic cytokine and/or growth factor-mediated, but not normal/unstimulated, fibroblast proliferation, differentiation and matrix production. Furthermore, relaxin augments matrix degradation through its ability to up-regulate the release and activation of various matrix-degrading matrix metalloproteinases and/or being able to down-regulate tissue inhibitor of metalloproteinase activity. Relaxin can also indirectly suppress fibrosis through its other well-known (anti-inflammatory, antioxidant, antihypertrophic, anti-apoptotic, angiogenic, wound healing and vasodilator) properties. This review will outline the organ-specific and general anti-fibrotic significance of exogenously administered relaxin and its mechanisms of action that have been documented in various non-reproductive organs such as the cardiovascular system, kidney, lung, liver, skin and tendons. In addition, it will outline the influence of sex on relaxin's anti-fibrotic actions, highlighting its potential as an emerging anti-fibrotic therapeutic. LINKED ARTICLESThis article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc Abbreviations α-SMA, α-smooth muscle actin; AT 2 receptor, angiotensin type 2 receptor; CCl 4 , carbon tetrachloride; ECM, extracellular matrix; HSC, hepatic stellate cell; INSL, insulin-like; KO, knockout; MSC, mesenchymal stem cell; PMA, phorbol 12-myristate 13-acetate; RLN, relaxin gene; rhRLX, synthetically or recombinantly produced drug form of relaxin; RXFP1, relaxin family peptide receptor 1; TIMP, tissue inhibitor of metalloproteinase IntroductionThe tissue response to stress depends on a number of intrinsic and extrinsic factors including the length and extent of injury. When injury or disease is mild or transient, then the tissue response leads to remodelling or regeneration of the organ parenchyma. However, if the injury is either severe or prolonged, the process is characterized by ongoing inflammation and extracellular matrix (ECM) production. Fibrosis is therefore a failure of the wound healing process, where ECM synthesis is ongoing (Wynn, 2008;Hewitson, 2009). This maladaptive response is particularly dependent on paracrine and autocrine production of TGF-β1 and the consequent recruitment of activated fibroblasts (myofibroblasts). Over-abundant ECM production and failure to resolve lead to significant organ damage and dysfunction, wh...

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Section: Anti‐fibrotic Effects Of Relaxin On the Integumentary Systemmentioning

confidence: 99%

Anti‐fibrotic actions of relaxin

Samuel

Royce

Hewitson

et al. 2016

British J Pharmacology

119

115

View full text Add to dashboard Cite

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“…All the experiments were performed three times in duplicate (passages 3 to 9). The time-point of the relaxin effect was chosen out of three (6, 12, and 24 h, data not shown), consistent with the literature [ 96 , 97 , 98 , 99 , 100 ]. The time point of 24 h was the one causing the strongest response, which was visible in the analyzed genes expressions (viability— Figure S2 ).…”

Section: Methodsmentioning

confidence: 99%

Relaxin Affects Airway Remodeling Genes Expression through Various Signal Pathways Connected with Transcription Factors

Wieczfińska

Pawliczak

2022

IJMS

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Fibrosis is one of the parameters of lung tissue remodeling in asthma. Relaxin has emerged as a natural suppressor of fibrosis, showing efficacy in the prevention of a multiple models of fibrosis. Therefore, the aim of this study was to analyze the aptitudes of relaxin, in the context of its immunomodulatory properties, in the development of airway remodeling. WI-38 and HFL1 fibroblasts, as well as epithelial cells (NHBE), were incubated with relaxin. Additionally, remodeling conditions were induced with two serotypes of rhinovirus (HRV). The expression of the genes contributing to airway remodeling were determined. Moreover, NF-κB, c-Myc, and STAT3 were knocked down to analyze the pathways involved in airway remodeling. Relaxin decreased the mRNA expression of collagen I and TGF-β and increased the expression of MMP-9 (p < 0.05). Relaxin also decreased HRV-induced expression of collagen I and α-SMA (p < 0.05). Moreover, all the analyzed transcription factors—NF-κB, c-Myc, and STAT3—have shown its influence on the pathways connected with relaxin action. Though relaxin requires further study, our results suggest that this natural compound offers great potential for inhibition of the development, or even reversing, of factors related to airway remodeling. The presented contribution of the investigated transcription factors in this process additionally increases its potential possibilities through a variety of its activity pathways.

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Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

Chi

Zhang

et al. 2017

Biochemical and Biophysical Research Communications

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Pretreatment with Relaxin Does Not Restore NO-Mediated Modulation of Calcium Signal in Coronary Endothelial Cells Isolated from Spontaneously Hypertensive Rats

Cited by 6 publications

References 30 publications

Anti‐fibrotic actions of relaxin

Anti‐fibrotic actions of relaxin

Relaxin Affects Airway Remodeling Genes Expression through Various Signal Pathways Connected with Transcription Factors

Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

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