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Bone morphogenetic protein-5 and early endothelial outgrowth cells (eEOCs) in acute ischemic kidney...

Bibliographic Details
Journal Title: American Journal of Physiology-Renal Physiology
Authors and Corporations: Patschan, Daniel, Schwarze, Katrin, Lange, Andrea, Meise, Nyree, Henze, Elvira, Becker, Jan Ulrich, Patschan, Susann, Müller, Gerhard A.
In: American Journal of Physiology-Renal Physiology, 305, 2013, 3, p. F314-F322
Media Type: E-Article
Language: English
American Physiological Society
Abstract: <jats:p> Early endothelial outgrowth cells (eEOCs) reproducibly have been shown to act protectively in acute ischemic kidney injury (AKI) and chronic kidney injury. Bone morphogenetic protein-5 (BMP-5) acted antifibrotically in human hypertensive nephropathy. The aim of the curent study was to analyze effects of BMP-5 treatment in an eEOC-based therapy of murine AKI and 5/6-nephrectomy. Male C57/Bl6N mice were either subjected to unilateral renal artery clamping postuninephrectomy or to 5/6-nephrectomy. Untreated or BMP-5-pretreated murine eEOCs were injected into recipient animals at the time of reperfusion (AKI) or at 2 and 5 days after 5/6-nephrectomy. Analysis of renal function and morphology was performed at 48 h and at 6 wk (AKI) or at 8 wk (5/6 model). Cellular consequences of eEOC treatment were evaluated using different in vitro assays. AKI was mitigated significantly by injecting BMP-5-pretreated eEOCs. Renal function was improved at 48 h and at 6 wk after cell therapy. In 5/6-nephrectomy, the cells failed to protect renal function, but proteinuria was reduced after administering untreated eEOCs. BMP-5 pretreatment resulted in aggravated proteinuria and renal fibrosis. In 5/6-nephrectomized animals, percentages of anti-smooth muscle actin+/CD31+ cells increased, indicating endothelial-mesenchymal transition (EnMT). In vitro analysis revealed increased cell migration and reduced cell apoptosis/necrosis. Paracrinic activity remained unaffected. BMP-5 acts as a potent eEOC agonist in murine AKI in the short and mid to long term. Cell effects in 5/6-nephrectomy are heterogenous, but untreated cells act antiproteinurically and antifibrotically without any impact on EnMT. </jats:p>
Physical Description: F314-F322
ISSN: 1931-857X
DOI: 10.1152/ajprenal.00677.2012