Diabetic nephropathy (DN) is one of the most serious and major renal complications of diabetes. Previously, Six-transmembrane Protein of Prostate 2 (STAMP2) was reported to contribute to nutritional stress. The purpose of this study is to investigate whether overexpression of STAMP2 attenuates diabetic renal injuries in DN rats. We induced the DN rat model by high-fat diet and low-dose streptozotocin and evaluated the metabolite and urine albumin/creatinine. Recombinant adeno-associated virus vectors were injected for overexpression of STAMP2. Pathophysiologic and ultrastructure features of DN by histochemical stain and transmission electron microscope, autophagy-related proteins and signaling pathway by western blotting were assessed. We found the expression of STAMP2 was decreased and autophagy was blunted in DN rat kidneys. Overexpressing STAMP2 significantly ameliorated metabolic disturbance, insulin resistance, and specifically restoring diabetic renal injury. Furthermore, overexpressing STAMP2 improved the autophagy deficiency in DN rats, as revealed by changes in the expressions of Beclin1, p62, and LC3. Furthermore, STAMP2 overexpressing promoted autophagy by inhibiting the mTOR and activating the AMPK/SIRT1 signaling pathway. Our results suggested that STAMP2 overexpression attenuated renal injuries via upregulating autophagy in DN rats. STAMP2 overexpressing promoted autophagy may been involved with inhibition of the mTOR/ULK1 and activation of the AMPK/SIRT1 signaling pathway.

糖尿病肾病（DN）是糖尿病最严重和主要的肾脏并发症之一。此前，据报道前列腺 2 的六跨膜蛋白 (STAMP2) 会导致营养压力。本研究的目的是研究 STAMP2 的过表达是否能减轻 DN 大鼠的糖尿病肾损伤。我们通过高脂肪饮食和低剂量链脲佐菌素诱导 DN 大鼠模型，并评估代谢物和尿白蛋白/肌酐。注射重组腺相关病毒载体用于过表达 STAMP2。通过组织化学染色和透射电子显微镜评估DN的病理生理学和超微结构特征，通过蛋白质印迹评估自噬相关蛋白和信号通路。我们发现 DN 大鼠肾脏中 STAMP2 的表达降低并且自噬减弱。过表达 STAMP2 显着改善代谢紊乱、胰岛素抵抗，特别是恢复糖尿病肾损伤。此外，如 Beclin1、p62 和 LC3 表达的变化所揭示的，过表达 STAMP2 改善了 DN 大鼠的自噬缺陷。此外，过表达 STAMP2 通过抑制 mTOR 和激活 AMPK/SIRT1 信号通路促进自噬。我们的结果表明，STAMP2 过表达通过上调 DN 大鼠的自噬来减轻肾损伤。STAMP2 过表达促进自噬可能与 mTOR/ULK1 的抑制和 AMPK/SIRT1 信号通路的激活有关。正如 Beclin1、p62 和 LC3 表达的变化所揭示的那样，过表达 STAMP2 改善了 DN 大鼠的自噬缺陷。此外，过表达 STAMP2 通过抑制 mTOR 和激活 AMPK/SIRT1 信号通路促进自噬。我们的结果表明，STAMP2 过表达通过上调 DN 大鼠的自噬来减轻肾损伤。STAMP2 过表达促进自噬可能与 mTOR/ULK1 的抑制和 AMPK/SIRT1 信号通路的激活有关。正如 Beclin1、p62 和 LC3 表达的变化所揭示的那样，过表达 STAMP2 改善了 DN 大鼠的自噬缺陷。此外，过表达 STAMP2 通过抑制 mTOR 和激活 AMPK/SIRT1 信号通路促进自噬。我们的结果表明，STAMP2 过表达通过上调 DN 大鼠的自噬来减轻肾损伤。STAMP2 过表达促进自噬可能与 mTOR/ULK1 的抑制和 AMPK/SIRT1 信号通路的激活有关。