心肾综合征(CRS)的发病率和死亡率高，但目前缺乏有效的治疗措施，阐明CRS的分子病理机制是研发CRS防治措施的基础。本研究将探讨慢性肾脏病起因的心肌细胞损伤的机制。我们已有的研究发现miR-30在足细胞高表达，通过调控Calcium/Calcineurin通路发挥足细胞保护作用。继而我们查询数据库发现心肌细胞同样高表达miR-30；体外细胞实验发现FGF23和AngII能够下调miR-30表达，降低miR-30能够激活Calcium/Calcineurin通路并导致心肌肥大。本研究的假说是：慢性肾脏病(已知循环FGF23/AngII升高)→心肌miR-30s 下调→Calcium/Calcineurin激活→心肌损伤。我们将利用体外细胞培养、转基因动物和疾病模型验证该通路，从而阐明CRS发生的新机制。对慢性肾脏病此通路进行干预，尤其阻止 miR-30s 下调，可能成为CRS治疗的新策略。

Cardio-renal syndrome (CRS) is a kind of clinical conditions in which cardiac and renal dysfunctions coexist. The morbidity and mortality of CRS is high, however, effective therapies are absent. Elucidation of the molecular pathogenesis is the basis for the development of strategies for CRS prevention and treatment. Here, we will investigate the pathogenesis of myocardial injury induced by chronic kidney diseases (CKD). Our previous studies showed that miR-30, highly expressed in podocytes, downregulated Calcium/Calcineurin signaling to protect podocyte from injury. By MIRZ database and primary experiments, we also found that cardiac myocyte has a high level of miR-30, which could be downregulated by FGF23/AngII, and downregulation of miR-30 activated Calcium/Calcineurin signal pathway leading to cardiomyocyte hypertrophy. Therefore, our hypothesis is follows: increased AngII/FGF23 in circulation of CKD→ cardiomyocyte miR-30s reduction→ Calcium/Calcineurin activation→ cardiac injury. We will conduct the studies including in vitro cardiomyocyte culture, transgenic mice and animal models to validate the hypothesis. The project will explore a novel mechanism of cardiac injury in CKD. The intervention of the signaling, especially inhibiting miR-30s decrease, may be a novel strategy for CRS therapy.