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dc.contributor.authorShi, W.
dc.contributor.authorMa, H.
dc.contributor.authorLin, J.
dc.date.accessioned2020-03-25T14:53:16Z
dc.date.available2020-03-25T14:53:16Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85081745317&doi=10.1111%2fjcmm.15147&partnerID=40&md5=3eacee5e9f4b808108ffd3d778456582
dc.identifier.urihttp://hdl.handle.net/10713/12383
dc.description.abstractThe role of IL-6 signalling in hypertensive heart disease and its sequelae is controversial. Our group demonstrated that Bazedoxifene suppressed IL-6/gp130 signalling in cancer cells but its effect on myocardial pathology induced by pressure overload is still unknown. We explored whether Bazedoxifene could confer benefits in wild-type C57BL/6J mice suffering from transverse aortic constriction (TAC) and the potential mechanisms in H9c2 myoblasts. Mice were randomized into three groups (Sham, TAC, TAC+Bazedoxifene, n = 10). Morphological and histological observations suggested TAC aggravated myocardial remodelling while long-term intake of Bazedoxifene (5 mg/kg, intragastric) attenuated pressure overload-induced pathology. Echocardiographic results indicated Bazedoxifene rescued cardiac function in part. We found Bazedoxifene decreased the mRNA expression of IL-6, MMP2, Col1A1, Col3A1 and periostin in murine hearts after 8-week surgery. By Western blot detection, we found Bazedoxifene exhibited an inhibition of STAT3 activation in mice three hours and 8 weeks after TAC. Acute TAC stress (3 hours) led to down-regulated ratio of LC3-Ⅱ/LC3-Ⅰ, while in mice after long-term (8 weeks) TAC this ratio becomes higher than that in Sham mice. Bazedoxifene inverted the autophagic alteration induced by TAC at both two time-points. In H9c2 myoblasts, Bazedoxifene suppressed the IL-6-induced STAT3 activation. Moreover, IL-6 reduced the ratio of LC3-Ⅱ/LC3-Ⅰ, promoted P62 expression but Bazedoxifene reversed both changes in H9c2 cells. Our data suggested Bazedoxifene inhibited IL-6/gp130 signalling and protected against cardiac remodelling together with function deterioration in TAC mice. Copyright 2020 The Authors.en_US
dc.description.urihttps://doi.org/10.1111/jcmm.15147en_US
dc.language.isoen_USen_US
dc.publisherBlackwell Publishing Inc.en_US
dc.relation.ispartofJournal of Cellular and Molecular Medicine
dc.subjectBazedoxifeneen_US
dc.subjectcardiac remodellingen_US
dc.subjectinterleukin-6en_US
dc.subjecttransverse aortic constrictionen_US
dc.titleInhibition of Interleukin-6/glycoprotein 130 signalling by Bazedoxifene ameliorates cardiac remodelling in pressure overload miceen_US
dc.typeArticleen_US
dc.identifier.doi10.1111/jcmm.15147
dc.identifier.pmid32164044


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