间充质干细胞
细胞生物学
体内
糖尿病肾病
链脲佐菌素
细胞凋亡
化学
体外
线粒体
癌症研究
生物
肾
糖尿病
内分泌学
生物化学
生物技术
作者
Naoto Konari,Kanna Nagaishi,Satoshi Kikuchi,Mineko Fujimiya
标识
DOI:10.1038/s41598-019-40163-y
摘要
Abstract The underlying therapeutic mechanism of renal tubular epithelium repair of diabetic nephropathy (DN) by bone marrow-derived mesenchymal stem cells (BM-MSCs) has not been fully elucidated. Recently, mitochondria (Mt) transfer was reported as a novel action of BM-MSCs to rescue injured cells. We investigated Mt transfer from systemically administered BM-MSCs to renal proximal tubular epithelial cells (PTECs) in streptozotocin (STZ)-induced diabetic animals. BM-MSCs also transferred their Mt to impaired PTECs when co-cultured in vitro , which suppressed apoptosis of impaired PTECs. Additionally, BM-MSC-derived isolated Mt enhanced the expression of mitochondrial superoxide dismutase 2 and Bcl-2 expression and inhibited reactive oxygen species (ROS) production in vitro . Isolated Mt also inhibited nuclear translocation of PGC-1α and restored the expression of megalin and SGLT2 under high glucose condition (HG) in PTECs. Moreover, isolated Mt directly injected under the renal capsule of STZ rats improved the cellular morphology of STZ-PTECs, and the structure of the tubular basement membrane and brush border in vivo . This study is the first to show Mt transfer from systemically administered BM-MSCs to damaged PTECs in vivo , and the first to investigate mechanisms underlying the potential therapeutic effects of Mt transfer from BM-MSCs in DN.
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