The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway

Abstract

The aim of the present study was to investigate the effect of urantide on collagen metabolism in the hearts of rats with atherosclerosis (aS) by evaluating the expression of Janus kinase 2 (JaK2)/signal transducer and activator of transcription 3 (STaT3) pathway constituents. urantide was delivered to rats with aS via tail vein injection for 3, 7 and 14 days. Serological indicators were identified by an automated biochemical analyzer. Histomorphological changes in the cardiac tissue of rats were observed by pathological staining techniques. The expression of genes and proteins was assessed using reverse transcription-quantitative Pcr and western blot analysis, respectively. localization of proteins was detected by immunofluorescence. overexpression of urotensin ii (uii) and its receptor, G protein-coupled receptor 14 (GPr14), was observed in the hearts of rats with AS and the expression of both proteins significantly declined after urantide administration. Triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein and calcium levels were improved in rats with aS following treatment with urantide. notably, urantide was able to antagonize the uii/GPr14 system. urantide treatment resulted in markedly decreased expression levels of matrix metalloproteinase 2 (MMP-2), collagen type i/iii, and genes and proteins in the JaK2/STaT3 pathway. By contrast, TiMP metallopeptidase inhibitor 2 (TiMP-2) levels were increased. in addition, the MMP-2/TIMP-2 protein ratio was significantly decreased in rats treated with urantide compared with aS rats with no urantide treatment. constituents of the JaK2/STaT3 pathway and collagen type i/iii were found to be localized in the diseased tissue and blood vessels of the hearts of rats with aS. in conclusion, urantide was able to effectively block the uii/GPr14 system by regulating the JaK2/STaT3 pathway and collagen metabolism. inhibition of the uii/GPr14 system may prevent and potentially treat atherosclerotic myocardial fibrosis. Based on the current results, it was hypothesized that collagen metabolism may be associated with the JaK2/STaT3 pathway.

Urantide decreases hepatic steatosis in rats with experimental atherosclerosis via the MAPK/Erk/JNK pathway

“…At present, to the best of our knowledge, only the authors' research team has provided a small amount of evidence indicating that urantide blocks the effects of UII on promoting the occurrence and development of AS ( 10 , 11 ). Concurrently, as shown in our previous studies using an AS rat model, urantide exerted protective effects on myocardial collagen metabolism disorder ( 34 ) and kidney injury ( 35 ), and the survival rate of rats with AS was also greatly improved by injecting with 30 µg/kg urantide. As to whether human patients are suitable for this dose, it is necessary to determine the best dose for patients by converting the equivalent dose between animals and humans.…”

N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1

“…The positive regulatory effect of METTL3 on JAK2 expression and JAK2/STAT3 pathway also has been identified by a prior study, which demonstrated that METTL3 knockdown inhibited cell self-renewal and induced cell differentiation by reducing JAK2 expression and inactivating the JAK2/STAT3 pathway in porcine induced pluripotent stem cells ( Wu et al, 2019 ). Moreover, JAK2/STAT3 signaling pathway has been found to be implicated in the pathogenesis of AS ( Wang et al, 2020c ; Wang et al, 2020d ). For example, the inhibition of JAK2/STAT3 signaling by JAK2 inhibitor Ruxolitinib inhibited AS progression, alleviated lipid and calcium burdens, and weakened proinflammatory responses in AS rabbits ( Yang et al, 2020 ).…”