Downregulated lncRNA-MIAT confers protection against erectile dysfunction by downregulating lipoprotein lipase via activation of miR328a-5p in diabetic rats

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1865

Article

Huo, Wei¹  Hou, Yi¹  Li, Yang¹  Li, Hai¹ 

[1] Jilin Univ, China Japan Union Hosp, Dept Urol, 126 Xiantai St, Changchun 130021, Jilin, Peoples R China

关键词: Diabetes;    Erectile dysfunction;    microRNA-328a-5p;    Long noncoding;    RNA myocardial infarction associated;    transcript;    Lipoprotein lipase;    Smooth muscle cells;    Endothelial cells;   

DOI  :  10.1016/j.bbadis.2019.01.018

来源: Elsevier

【 摘 要 】

Erectile dysfunction (ED) is a common comorbidity in males with diabetes. In this study, we aimed to investigate how IncRNA-MIAT affects ED in diabetes and the involved mechanism. Microarray analysis was performed to screen ED-related differentially expressed genes, regulatory microRNA (miR) and long noncoding RNA (IncRNA). Highly expressed lipoprotein lipase (LPL) was identified, and subsequently miR-328a-5p and IncRNAMIAT were determined. Diabetes was induced by streptozotocin in rats, and diabetic rats with ED were selected. Vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were cocultured. The siRNA against IncRNA-MIAT, miR-328a-5p mimic and overexpression vector of LPL were transfected to investigate the specific effects of miR-328a-5p, IncRNA-MIAT and LPL on ED in diabetes. The expression of LPL, IncRNA-MIAT and miR328a-5p in the serum of diabetic patients was measured. Increased LPL and IncRNA-MIAT and reduced miR328a-5p were observed in diabetic patients. In addition, ED led to upregulated LPL and IncRNA-MIAT and downregulated miR-328a-5p in serum of diabetic patients and VSMCs of diabetic rats, especially in those with ED. LncRNA-MIAT directly regulated miR-328a-5p, which directly targeted LPL. LncRNA-MIAT upregulated LPL by acting as a ceRNA of miR-328a-5p. Silencing of IncRNA-MIAT and LPL or miR-328a-5p overexpression reduced VEC apoptosis and increased cell proliferation. In addition, an increased intracavemosal pressure (ICP)/ mean arterial pressure (MAP) ratio was noted in the corpus cavemosum of rats and inhibited VEC injury. Taken together, our data demonstrated that depleted IncRNA-MIAT suppressed LPL by increasing miR-328a-5p, thereby inhibiting VEC injury to attenuate ED in diabetic rats.

【 授权许可】

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