Introduction

Diabetic kidney disease (DKD) has become the primary cause of chronic renal failure in China, and renal tubulointerstitial fibrosis plays a central role in DKD progression. Urinary exosomes, which reflect kidney changes, are largely influenced by RNA-binding proteins (RBPs) in their miRNA content.

Objectives

Our research aimed to determine the effect of the RNA-binding protein RBMX on exosomal miRNA in DKD.

Methods

We introduced a higher level of Rbmx into diabetic mice using an adenoassociated virus and isolated exosomes from their kidney tissue through advanced centrifugation techniques and specialized kits. We then conducted a series of tests, including qRT-PCR, Western blot, MitoSOX, ATP luminescence, coimmunoprecipitation, SUMOylation assays, RNA immunoprecipitation, and confocal microscopy.

Results

RBMX is found in higher levels in DKD and contributes to worsening kidney fibrosis, mitochondrial damage, and miRNA mismanagement in exosomes. It specifically binds with miR-26a, miR-23c, and miR-874 within the exosomes. This dysfunction may be linked to changes in RBMX SUMOylation. These miRNAs seem to protect against mitochondrial damage in kidney cells by targeting CERS6.

Conclusion

DeSUMOylation of RBMX plays a crucial role in determining the makeup of miRNAs in kidney cell exosomes, impacting the protective miRNAs which regulate mitochondrial damage through their interaction with CERS6 mRNA, ultimately affecting mitochondrial health in DKD.

中文翻译：

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RBMX 的去SUMO化调节货物的外泌体分选，促进糖尿病肾病中的肾小管间质纤维化。


引言糖尿病肾病（DKD）已成为我国慢性肾功能衰竭的主要原因，而肾小管间质纤维化在DKD进展中发挥着核心作用。尿液外泌体反映了肾脏的变化，其 miRNA 含量很大程度上受到 RNA 结合蛋白 (RBP) 的影响。目的 我们的研究旨在确定 RNA 结合蛋白 RBMX 对 DKD 中外泌体 miRNA 的影响。方法我们使用腺相关病毒将较高水平的 Rbmx 引入糖尿病小鼠中，并通过先进的离心技术和专用试剂盒从其肾组织中分离出外泌体。然后我们进行了一系列测试，包括 RT-qPCR、Western blot、MitoSOX、ATP 发光、免疫共沉淀、SUMOylation 测定、RNA 免疫沉淀和共聚焦显微镜。结果 RBMX 在 DKD 中含量较高，并导致肾纤维化恶化、线粒体损伤和外泌体中 miRNA 管理不当。它与外泌体内的 miR-26a、miR-23c 和 miR-874 特异性结合。这种功能障碍可能与 RBMX SUMOylation 的变化有关。这些 miRNA 似乎可以通过靶向 CERS6 来防止肾细胞中的线粒体损伤。结论 RBMX 的去SUMO化在决定肾细胞外泌体中 miRNA 的组成中起着至关重要的作用，影响通过与 CERS6 mRNA 相互作用调节线粒体损伤的保护性 miRNA，最终影响 DKD 中的线粒体健康。