Diabetic nephropathy (DN) is an increasing threat to human health and is regarded as an important public issue. The pathophysiologic mechanisms of DN are complicated. The initiating molecular events triggering the loss function in mesangial cells (MCs) in DN are not well known. In this cross-disciplinary study, transcriptome analysis of high glucose (HG)-treated mouse MCs (MMCs) using next-generation sequencing and systematic bioinformatics analyses indicated that miR-15b-5p and its downstream target B cell lymphoma 2 (BCL-2) contribute to HG-induced apoptosis in MMCs. HG elevated miR-15b-5p expression, which in turn decreased the translation of BCL-2, leading to MMC apoptosis under HG. Apoptosis of MCs was enhanced in the presence of extracellular vesicles isolated from the urine of type 2 diabetic patients with high levels of miR-15b-5p. Furthermore, increased levels of urinary miR-15b-5p were found in db/db mice and type 2 diabetic patients, and such levels correlated with low baseline kidney function and rapid decline in kidney function during a mean of follow-up period of 2.4 ± 0.1 years. Therefore, miR-15b-5p induced mesangial cells apoptosis by targeting BCL-2 under HG. miR-15b-5p has the potential to predict kidney injury in DN. Blocking the miR-15b-5p epigenetic regulatory network could be a potential therapeutic strategy to prevent mesangial apoptosis in DN.

中文翻译：

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高糖通过miR-15b-5p诱导肾小球膜细胞凋亡，并通过细胞外囊泡转运促进糖尿病性肾病。

糖尿病肾病（DN）对人类健康的威胁越来越大，被认为是重要的公共问题。DN的病理生理机制复杂。引发DN肾小球系膜细胞（MCs）丧失功能的分子启动事件尚不清楚。在这项跨学科研究中，使用下一代测序和系统生物信息学分析对高糖（HG）处理的小鼠MC（MMC）进行转录组分析表明，miR-15b-5p及其下游靶B细胞淋巴瘤2（BCL-2 ）有助于HG诱导MMCs凋亡。HG升高了miR-15b-5p表达，进而降低了BCL-2的翻译，导致HG下MMC凋亡。从具有高水平miR-15b-5p的2型糖尿病患者尿液中分离出细胞外囊泡，MC的凋亡得以增强。此外，在db / db小鼠和2型糖尿病患者中发现尿中miR-15b-5p的水平升高，且该水平与平均基线随访期间肾功能低和肾功能快速下降相关，为2.4± 0.1年。因此，miR-15b-5p通过在HG下靶向BCL-2诱导系膜细胞凋亡。miR-15b-5p具有预测DN肾损伤的潜力。阻断miR-15b-5p表观遗传调控网络可能是预防DN系膜细胞凋亡的潜在治疗策略。miR-15b-5p通过在HG下靶向BCL-2诱导系膜细胞凋亡。miR-15b-5p具有预测DN肾损伤的潜力。阻断miR-15b-5p表观遗传调控网络可能是预防DN系膜细胞凋亡的潜在治疗策略。miR-15b-5p通过在HG下靶向BCL-2诱导系膜细胞凋亡。miR-15b-5p具有预测DN肾损伤的潜力。阻断miR-15b-5p表观遗传调控网络可能是预防DN系膜细胞凋亡的潜在治疗策略。