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miR-218 Expressed in Endothelial Progenitor Cells Contributes to the Development and Repair of the Kidney Microvasculature.
Wang, Xiaojie; Liu, Jialing; Yin, Wenqing; Abdi, Farhiya; Pang, Paul D; Fucci, Quynh-Anh; Abbott, Molly; Chang, Steven L; Steele, Graeme; Patel, Ankit; Mori, Yutaro; Zhang, Aifeng; Zhu, Shikai; Lu, Tzong-Shi; Kibel, Adam S; Wang, Bin; Lim, Kenneth; Siedlecki, Andrew M.
Afiliação
  • Wang X; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China.
  • Liu J; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Nephrology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Yin W; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Abdi F; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Pang PD; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Fucci QA; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Abbott M; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Chang SL; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Steele G; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Patel A; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Mori Y; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Zhang A; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Zhu S; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Lu TS; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Kibel AS; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Wang B; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Lim K; Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • Siedlecki AM; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: asiedlecki@partners.org.
Am J Pathol ; 190(3): 642-659, 2020 03.
Article em En | MEDLINE | ID: mdl-31972158
Ischemia due to hypoperfusion is one of the most common forms of acute kidney injury. We hypothesized that kidney hypoxia initiates the up-regulation of miR-218 expression in endothelial progenitor cells (EPCs) to guide endocapillary repair. Murine renal artery-derived EPCs (CD34+/CD105-) showed down-regulation of mmu-Mir218-5p/U6 RNA ratio after ischemic injury, while in human renal arteries, MIR218-5p expression was up-regulated after ischemic injury. MIR218 expression was clarified in cell culture experiments in which increases in both SLIT3 and MIR218-2-5p expressions were observed after 5 minutes of hypoxia. ROBO1 transcript, a downstream target of MIR218-2-5p, showed inverse expression to MIR218-2-5p. EPCs transfected with a MIR218-5p inhibitor in three-dimensional normoxic culture showed premature capillary formation. Organized progenitor cell movement was reconstituted when cells were co-transfected with Dicer siRNA and low-dose Mir218-5p mimic. A Mir218-2 knockout was generated to assess the significance of miR-218-2 in a mammalian model. Mir218-2-5p expression was decreased in Mir218-2-/- embryos at E16.5. Mir218-2-/- decreased CD34+ angioblasts in the ureteric bud at E16.5 and were nonviable. Mir218-2+/- decreased peritubular capillary density at postnatal day 14 and increased serum creatinine after ischemia in adult mice. Systemic injection of miR-218-5p decreased serum creatinine after injury. These experiments demonstrate that miR-218 expression can be triggered by hypoxia and modulates EPC migration in the kidney.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Imunológicos / MicroRNAs / Injúria Renal Aguda / Isquemia / Proteínas do Tecido Nervoso Limite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Pathol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Imunológicos / MicroRNAs / Injúria Renal Aguda / Isquemia / Proteínas do Tecido Nervoso Limite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Pathol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China