title: miR-21-containing microvesicles from injured tubular epithelial cells promote tubular phenotype transition by targeting PTEN protein.
abstract: Renal fibrosis is inevitably progressive no matter what the initial insult is or whether the insult persists. In an experimental fibrosis model induced by unilateral ureteral obstruction, the accelerated pathological changes could hardly be explained by aggravated pressure caused by hydronephrosis after ligation. Moreover, at the initial stage, tubular phenotype transition and matrix deposition in obstructive kidneys are always local and scattered; however, these renal lesions expand and progress with time. In this study, cultured recipient tubular cells underwent phenotype transition after incubation with conditioned media derived from transforming growth factor-β1-treated donor tubular cells. Thus, it is reasonable to speculate that some secretable molecules from injured tubules contribute to the progression of renal fibrosis. Herein, we report that secreted miRNA-21 (miR-21) can serve as the molecule mediating intercellular communication. miR-21 was packaged into microvesicles, which enter and deliver miR-21 into recipient tubular cells, and exogenous miR-21 enhances Akt signaling by target depression of phosphatase and tensin homolog (PTEN) protein, and promotes tubular phenotype transition. These results demonstrate that tubular cells can secrete miR-21 and deliver it into recipient tubules by microvesicles, where the exogenous miR-21 can target PTEN protein and enhance Akt signaling in recipient cells. Microvesicle-mediated delivery of miR-21 among tubular epithelial cells might shed new light on the mechanism of progressive renal fibrosis.
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Yang
authors: Y
authors: Zhou
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Mingxia
authors: M
authors: Xiong
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Li
authors: L
authors: Fang
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Lei
authors: L
authors: Jiang
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Ping
authors: P
authors: Wen
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Chunsun
authors: C
authors: Dai
authors: Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors: Chen-Yu
authors: CY
authors: Zhang
authors: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China. Electronic address: jwyang@njmu.edu.cn.
authors: Junwei
authors: J
authors: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism* / Q000652:urine; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C546082:mirn21 microRNA, rat; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D020782:Matrix Metalloproteinases