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 1

LVH gradually appears in SN rats.

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LVH gradually appears in SN rats. (A) Schematic diagram for continuous o...
(A) Schematic diagram for continuous observation in nephrectomized rats. (B) Representative short-axis echocardiography and M-mode images. (C and D) Diastolic interventricular septal thickness (IVS; d) and relative wall thickness of left ventricles gradually increase in nephrectomized rats. **P < 0.01 compared with values for the sham indicated by the dashed line, by 2-tailed, unpaired Student’s t test (C) and by Mann-Whitney U test (D). Data are shown as mean ± SD and median with interquartile range (C and D, respectively). n = 5 or 6 rats per group. (E) Diastolic LV internal diameter (LVID; d) decreases at 3 weeks after nephrectomy. *P < 0.05 compared with values for the sham indicated by the dashed line, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 or 6 rats per group. (F) Nephrectomy leads to LV ejection fraction increase at 3 weeks after nephrectomy. *P < 0.05 compared with values for the sham indicated by the dashed line, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 or 6 rats per group. (G–I) SN results in increase in heart weight/tibial length, LV weight/tibial length, and LV weight/heart weight ratios at 5 weeks after surgery. **P < 0.01 compared with values for the sham indicated by the dashed line, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 or 6 rats per group. (J) Nephrectomy leads to downregulation of cardiac miR-30. Expression levels are normalized by U6. *P < 0.05 and **P < 0.01 compared with values for the sham indicated by the dashed line, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 or 6 rats per group.