Inhibition of Interleukin‐6/glycoprotein 130 signalling by Bazedoxifene ameliorates cardiac remodelling in pressure overload mice
| Autor: | Tianshu Liu, Wei Shi, Sheng Li, Maocai Zhai, Shengqi Huo, Junyi Guo, Cuntai Zhang, Li Lin, Jiayuh Lin, Haiyan Ma, Chenglong Li, Pengcheng Luo, Dan Yan, Jiagao Lv, Jingwen Tao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cardiac function curve medicine.medical_specialty Indoles Bazedoxifene Periostin Mice 03 medical and health sciences 0302 clinical medicine transverse aortic constriction Internal medicine Autophagy Cytokine Receptor gp130 medicine Animals Humans Myocyte Interleukin 6 Pressure overload Ventricular Remodeling biology Interleukin-6 business.industry cardiac remodelling Heart Original Articles Cell Biology Glycoprotein 130 Rats Disease Models Animal 030104 developmental biology Endocrinology Gene Expression Regulation interleukin‐6 030220 oncology & carcinogenesis Hypertension Cancer cell biology.protein Molecular Medicine Original Article business medicine.drug |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | The 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. |
| Databáze: | OpenAIRE |
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