LncRNAs play important roles in the regulation of podocyte apoptosis in diabetic nephropathy (DN). However, the role of lncRNA SNHG17 in controlling mitophagy-induced apoptosis of podocytes in DN is unknown. This study aims to elucidate the underlying mechanism of lncRNA SNHG17 in the regulation of mitophagy-induced apoptosis of podocytes in DN. LncRNA SNHG17 and Mammalian Sterile 20-like kinase 1 (Mst1) expression were upregulated in glomeruli and podocytes of DM mice and high glucose-treated podocytes, whereas Parkin expression was downregulated. LncRNA SNHG17 overexpression suppressed mitophagy and induced apoptosis of podocytes while silencing lncRNA SNHG17 promoted mitophagy and reduced the apoptosis of podocytes. In addition, lncRNA SNHG17 interacted with Mst1 and regulated the degradation of Mst1. We further found lncRNA SNHG17 regulated Parkin expression through Mst1. Mechanistically, lncRNA SNHG17 regulated Parkin-dependent mitophagy and apoptosis of podocytes through regulating Mst1. Finally, silencing lncRNA SNHG17 promoted mitophagy and relieved DNin vivo. In conclusion, lncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through regulating the degradation of Mst1.

LncRNA 在糖尿病肾病 (DN) 足细胞凋亡的调节中发挥重要作用。然而，lncRNA SNHG17 在控制 DN 中线粒体自噬诱导的足细胞凋亡中的作用尚不清楚。本研究旨在阐明lncRNA SNHG17在调节线粒体自噬诱导的DN足细胞凋亡中的潜在机制。DM 小鼠的肾小球和足细胞以及高糖处理的足细胞中 LncRNA SNHG17 和哺乳动物不育 20 样激酶 1 (Mst1) 表达上调，而 Parkin 表达下调。LncRNA SNHG17过表达抑制线粒体自噬并诱导足细胞凋亡，而沉默lncRNA SNHG17则促进线粒体自噬并减少足细胞凋亡。此外，lncRNA SNHG17与Mst1相互作用并调节Mst1的降解。我们进一步发现lncRNA SNHG17通过Mst1调节Parkin表达。从机制上讲，lncRNA SNHG17通过调节Mst1来调节Parkin依赖性线粒体自噬和足细胞凋亡。最后，沉默lncRNA SNHG17可促进线粒体自噬并缓解体内DN 。总之，lncRNA SNHG17 敲低通过调节 Mst1 的降解促进 Parkin 依赖性线粒体自噬并减少足细胞凋亡。