scholarly journals Peptide hormone relaxin: from molecular effects to clinical results

Author(s):  
O. V. Prokhorova ◽  
A. A. Olina ◽  
G. Kh. Tolibova ◽  
T. G. Tral

Introduction. The peptide hormone relaxin, which is produced by cells of the corpus luteum during and outside pregnancy, has a huge number of clinically significant effects, mediating many biological mechanisms, including antifibrotic, vasodilatory, angiogenic, anti-inflammatory and antiapoptotic effects.Purpose of the study: based on the study of modern literature data, to analyze the results of scientific research, representing the current system of views on the physiological and pathophysilogical effects of relaxin.Materials and methods. A study f scientific publications for the period from 2005 to 2020 in e PubMed and Elibrary databases was carried out using the keywords: relaxin, pregnancy, relaxin signaling pathway, reproductive system, extracellular matrix.Results and Discussion. The study of modern views on the physiology of relaxin has shown that this hormone mediates its effects by binding to the specific receptor RXFP1, which is localized in a large number of reproductive nonproductive tissues. Relaxin performs many functions related to the remodeling of the extracellular matrix and vasculature. The main uterotropic effects of this peptide include stimulation of growth and vascularization of the uterus, remodeling of extracellular matrix components, and regulation of vascular endothelial growth factor in preparation for implantation.Conclusion. The progress of the last decade in understanding the biochemistry of the hormone relaxin has formed the basis for a deeper penetration into all the variety of its physiological roles. The participation of relaxin in the mechanisms of relaxation of the myometrium during pregnancy, remodeling of the connective tissue of target organs in the antenatal period creases its potential clinical significance. The prospect of a possible therapeutic use of relaxin preparations in stimulating antenatal transformation of the cervix, in vitro fertilization, therapy of preeclampsia, acute heart failure and myocardial ischemia turns it into a potential therapeutic agent for these pathological conditions.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Karien J Rodriguez ◽  
Kristyn S Masters

Calcification is the leading cause of bioprosthetic and native aortic valve failure, but relatively little is known regarding the factors that contribute to the progression of valvular calcification. Because extracellular matrix (ECM) disarray is often observed in explanted diseased valves, we have investigated the role of individual ECM components in the in vitro calcification of valvular interstitial cells (VICs). The transformation of VICs to an osteoblast-like phenotype was quantified in VICs cultured on different types of ECM coatings. The results show that the number and size of calcific nodules formed in VIC cultures, as well as the expression of mineralization markers alkaline phosphatase (ALP) and CBFa1, were highly dependent upon the composition of the culture surface. In fact, VICs cultured on certain ECM components, namely collagen (Coll) and fibronectin (FN), were resistant to calcification, even upon treatment with potent mineralization-inducing growth factors, such as transforming growth factor beta1 (TGFb1). Meanwhile, VIC cultures on fibrin (FB), laminin, and heparin not only had a high number of calcified nodules (p<0.001 vs. Coll, FN), but also elevated levels of ALP and CBFa1 (p<0.02), and the number of nodules on these ‘pro-calcific’ coatings significantly increased upon treatment with exogenous TGFb1 (p<0.05). To explain the ECM-dependence of calcification, the endogenous production of a pro-mineralization factor (TGFb1) was assessed in VICs on anti-calcific (Coll) and pro-calcific (FB) substrates. Quantification of TGFb1 mRNA revealed that VICs on Coll surfaces expressed a significantly lower amount of TGFb1 mRNA than VICs on FB (p<0.01). Furthermore, treatment with a neutralizing antibody to TGFb1 decreased TGFb1 mRNA expression by VICs on Coll in comparison to VICs on FB or polystyrene controls (p<0.02). Thus, we have discovered a strong correlation between VIC calcification and ECM composition. Our findings show that the ECM plays an important role in controlling TGFb1 expression and subsequent calcification of VICs, which may significantly impact the design of biomaterials for valve tissue engineering, understanding of valvular disease, and the development of preventative treatments for valve calcification.


2018 ◽  
Vol 314 (6) ◽  
pp. R753-R760 ◽  
Author(s):  
Maria Jelinic ◽  
Sarah A. Marshall ◽  
Dennis Stewart ◽  
Elaine Unemori ◽  
Laura J. Parry ◽  
...  

The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a “pleiotropic hormone.” Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion, and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies. In many cases, the positive outcomes from preclinical animal studies were not replicated in human clinical trials. Therefore, the focus of this review is to evaluate the various animal models used to develop relaxin as a potential therapeutic and consider the limitations that must be addressed in future studies. These include the use of human relaxin in animals, duration of relaxin treatment, and the appropriateness of the clinical conditions being considered for relaxin therapy.


2016 ◽  
Vol 36 (6) ◽  
Author(s):  
Karolina Janik ◽  
Marta Popeda ◽  
Joanna Peciak ◽  
Kamila Rosiak ◽  
Maciej Smolarz ◽  
...  

Primary breast and prostate epithelial cancer cells may be efficiently cultured in vitro using simple and easily validatable approach–plates coated with a mixture of extracellular matrix components and tissue-specific primary cell medium.


1984 ◽  
Vol 1 (1) ◽  
pp. 48-50 ◽  
Author(s):  
Per Sundstr�m ◽  
H�kan Wramsby ◽  
Percy Liedholm ◽  
Stig Kullander ◽  
Per-H�kan Persson ◽  
...  

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