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 3

Cardiac miR-30 rescue mitigates CKD-induced LVH.

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Cardiac miR-30 rescue mitigates CKD-induced LVH. (A and B) miR-30 inhibi...
(A and B) miR-30 inhibits the IVS; d and relative wall thickness of LV increases in nephrectomized rats. **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 = 6 rats per group. (C–E) miR-30 decreases heart weight/tibial length, LV weight/tibial length, and LV weight/heart weight ratios in SN rats. *P < 0.05 and **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 = 6 rats per group. (F) MiR-30 suppresses increased cross-sectional area of cardiomyocytes in nephrectomized rats. **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 median and quartiles, as well as the minimum and maximum values of the distribution. n = 360 cells per group. (G–J) miR-30 mitigates upregulated hypertrophic indicators in CKD rats, despite having no significant effect on α–myosin heavy chain (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 = 6 rats per group.