Ebrahim Nesrine, Ahmed Inas A, Hussien Noha I, Dessouky Arigue A, Farid Ayman Samir, Elshazly Amal M, Mostafa Ola, Gazzar Walaa Bayoumie El, Sorour Safwa M, Seleem Yasmin, Hussein Ahmed M, Sabry Dina
Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt.
Stem Cell Unit, Faculty of Medicine, Benha University, Benha 13518, QG, Egypt.
Cells. 2018 Nov 22;7(12):226. doi: 10.3390/cells7120226.
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes.
Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA.
We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.
糖尿病肾病（DN）是糖尿病的一种严重并发症，也是终末期肾病的常见病因。自噬对高血糖引起的肾脏损伤具有防御作用。间充质干细胞（MSC）衍生的外泌体目前被认为是治疗慢性肾损伤的一种新的有前景的疗法。然而，外泌体对DN的肾脏保护机制尚未完全明确。我们研究了MSC衍生的外泌体在增强自噬活性方面的潜在作用及其对DN的影响。在本研究中，我们使用了五组大鼠：对照组；糖尿病肾病组；外泌体治疗的糖尿病肾病组；3-甲基腺嘌呤（3-MA）和氯喹（自噬抑制剂）治疗的糖尿病肾病组；3-甲基腺嘌呤（3-MA）、氯喹和外泌体治疗的糖尿病肾病组。我们评估了肾功能、形态和纤维化情况。此外，还检测了自噬标志物雷帕霉素靶蛋白（mTOR）、Beclin-1、微管相关蛋白1轻链3（LC3-II）以及LC3-II/LC3-I的比值。另外，使用电子显微镜检测自噬体。
外泌体显著改善了肾功能，并使肾组织出现组织学恢复，肾组织中LC3和Beclin-1显著增加，mTOR和纤维化标志物表达显著降低。自噬抑制剂氯喹和3-MA部分消除了上述所有作用。
我们得出结论，外泌体诱导的自噬可减轻链脲佐菌素诱导的糖尿病大鼠模型中的糖尿病肾病。
