MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease
Jingfu Bao, Yinghui Lu, Qinying She, Weijuan Dou, Rong Tang, Xiaodong Xu, Mingchao Zhang, Ling Zhu, Qing Zhou, Hui Li, Guohua Zhou, Zhongzhou Yang, Shaolin Shi, Zhihong Liu, Chunxia Zheng
Jingfu Bao, Yinghui Lu, Qinying She, Weijuan Dou, Rong Tang, Xiaodong Xu, Mingchao Zhang, Ling Zhu, Qing Zhou, Hui Li, Guohua Zhou, Zhongzhou Yang, Shaolin Shi, Zhihong Liu, Chunxia Zheng
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Research Article Cardiology Nephrology

MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease

Abstract

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in patients with chronic kidney disease (CKD). miRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only resulted in LVH but also suppressed miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuated LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes led to cardiomyocyte hypertrophy by upregulating the calcineurin signaling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23, uremic toxin, angiotensin II, and transforming growth factor–β, suppressed cardiac miRNA-30 expression, while miRNA-30 supplementation blunted cardiomyocyte hypertrophy induced by such factors. These results uncover a potentially novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.

Authors

Jingfu Bao, Yinghui Lu, Qinying She, Weijuan Dou, Rong Tang, Xiaodong Xu, Mingchao Zhang, Ling Zhu, Qing Zhou, Hui Li, Guohua Zhou, Zhongzhou Yang, Shaolin Shi, Zhihong Liu, Chunxia Zheng

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Figure 10

miR-30 inhibits FGF-23–induced cardiac hypertrophy in vivo.

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miR-30 inhibits FGF-23–induced cardiac hypertrophy in vivo. (A) Schemati...
(A) Schematic diagram for FGF-23 and AAV2/9 injection. (B–D) AAV2/9-miR-30-Zsgreen treatment rescues the downregulation of cardiac miR-30 in FGF-23–treated mice. Expression levels are normalized by U6. **P < 0.01 compared with values indicated by the dashed line, by 1-way ANOVA test. Tukey’s multiple comparisons test was used for multiple comparison. Data are shown as mean ± SD. n = 4 mice per group. (E) Representative cross sections (hematoxylin and eosin staining; original magnification, ×20; scale bar: 200 μm) and WGA staining (original magnification, ×400; scale bar: 50 nm) of myocardium. (F) miR-30 rescue significantly reduces FGF-23–induced cardiomyocyte hypotrophy. **P < 0.01 compared with values indicated by the dashed line, by Kruskal-Wallis test. Dunn’s multiple comparisons test was used for multiple comparison. Data are shown as median and quartiles, as well as the minimum and maximum values of the distribution. n = 240 cells per group. (G and H) miR-30 mitigates upregulated hypertrophic indicators in FGF-23–treated mice, despite having no significant effect on α-Mhc. Expression levels are normalized by 18S. **P < 0.01 compared with values indicated by the dashed line, by 1-way ANOVA test. Tukey’s multiple comparisons test was used for multiple comparison. Data are shown as mean ± SD. n = 4 mice per group.