Navegando por Palavras-chave "Relaxin"

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    Avaliação do efeito antifibrótico da Relaxina: estudo in vivo e in vitro
    (Universidade Federal de São Paulo (UNIFESP), 2016-04-29) Figueiredo, Camila Médici de [UNIFESP]; Boim, Mirian Aparecida [UNIFESP]; http://lattes.cnpq.br/8916858915652849; http://lattes.cnpq.br/7061959978075667; Universidade Federal de São Paulo (UNIFESP)
    Mesangial cells (MC) and its extracellular matrix are relevant to the maintenance of glomerular filtration rate by modulating the surface available for filtration. Under stimuli such as high glucose, MC proliferate and become hypersecretory of matrix proteins and pro-fibrotic factors such as TGFβ1, contributing to glomerular sclerosis. A number of the strategies have been tested in order to reduce the fibrogenic process dependent of TGFβ1 and in this context, the pregnancy related hormone Relaxin (RLX) has been explored due to its antifibrotic capacity. Usually related to pregnancy, RLX was capable to reduce TGFβ1-induced fibrosis, and increase the secretion of metalloproteinases, which degrade matrix proteins. Thus, the objective of this study was to evaluate if high levels of endogenous RLX found during pregnancy would be able to reduce the fibrogenic process induced by unilateral ureteral obstruction (UUO). Pregnant rats, which have high levels of RLX were used. Seven days pregnant rats were submitted to UUO for 7 or 15 days. In addition to the in vivo fibrosis model, we also evaluated an in vitro model using primary mesangial cells cultured from virgin and pregnant rats. MC were cultured from kidney of pregnant and virgin rats, and stimulated with high glucose concentration (30 mM) and/or RLX (100ng/ml) for 48 hours. The Pregnant group showed to be more protected against the effects of UUO with less reduction in creatinine clearance and less interstitial collagen accumulation. In the in vitro model, high glucose stimulated the expression of RLX receptor (Rxfp1), Collagen and TGFβ1 in the Virgin group but had no effect in MC from pregnant rats. Treatment with RLX prevented these changes in Virgin group. Our results suggest that elevated levels of endogenous or exogenous RLX may have a protective role in fibrogenic process.
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    Intracellular signaling pathways involved in the relaxin-induced proliferation of rat Sertoli cells
    (Elsevier B.V., 2012-09-15) Nascimento, Aline Rosa [UNIFESP]; Pimenta, Maristela Taliari [UNIFESP]; Lucas, Thais Fabiana Gameiro [UNIFESP]; Royer, Carine [UNIFESP]; Porto, Catarina Segreti [UNIFESP]; Lazari, Maria de Fatima Magalhaes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Regulation of Sertoli cell number is a key event to determine normal spermatogenesis. We have previously shown that relaxin and its G-protein coupled receptor RXFP1 are expressed in rat Sertoli cells, and that relaxin stimulates Sertoli cell proliferation. This study examined the mechanisms underlying the mitogenic effect of relaxin in a primary culture of Sertoli cells removed from testes of immature rats. Stimulation with exogenous relaxin increased Sertoli cell number and the expression of the proliferating cell nuclear antigen (PCNA), but did not affect them RNA level of the differentiation markers cadherins 1 and 2. Relaxin-induced Sertoli cell proliferation was blocked by inhibition of MEK/ERK1/2 or PI3K/AKT pathways, but not by inhibition of PKC or EGFR activity. Relaxin induced a rapid and transient activation of ERK1/2 phosphorylation, which was MEK and SRC-dependent, and involved upstream activation of G(i). AKT activation could be detected 5 min after relaxin stimulation, and was still detected after 24 h of stimulation with relaxin. Relaxin-induced AKT phosphorylation was G(i)- but not PKA-dependent, and it was blocked by both PI3K and MEK inhibitors. in conclusion, the mitogenic effect of relaxin in Sertoli cell involves coupling to G(i) and activation of both MEK/ERK1/2 and PI3K/AKT pathways. (c) 2012 Elsevier B.V. All rights reserved.
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    Mesangial Cells Cultured from Pregnant Rats Display Reduced Reactivity to Angiotensin II: the Role of Relaxin, Nitric Oxide and AT2 Receptor
    (Karger, 2012-01-01) Carvalho, Lucimeire Nova de [UNIFESP]; Cristovam, Priscila Cardoso [UNIFESP]; Passos, Clévia dos Santos [UNIFESP]; Boim, Mirian Aparecida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background/Aims: Pregnancy is characterized by vasodilatation and increased glomerular filtration rate (GFR), despite overstimulation of the renin angiotensin system (RAS). the mesangial cells (MCs) influences GFR and when cultured from pregnant rats displays refractoriness to Ang II. We evaluated the role of relaxin (RLX) and its receptor (RXFP1), nitric oxide (NO) and the AT2 receptor in this response. Methods: MCs cultured from kidneys of virgin (V) and pregnant (P) Wistar rats were treated with RLX or AT2 receptor blocker PD123319 or NO synthase inhibitor L-NAME. After 24 hr, intracellular calcium concentration ([Ca]i) was recorded before and after the addition of Ang II. Results: MCs from V group expressed AT2, RLX and RXFP1, whose levels were increased in P cells. Ang II induced a 150% increase in [Ca]i in the V cells and 85% (p<0.05) in the P cells. V cells treated with RLX displayed a similar response to that observed in P cells, suggesting that RLX can modulate the reactivity of the MCs to Ang II. L-NAME and PD123319 did not interfere in this response. Conclusion: Results suggest that RLX is a mediator of the refractoriness of the MCs to Ang II during pregnancy. Copyright (c) 2012 S. Karger AG, Basel