title: The endothelial-to-mesenchymal transition and endothelial cilia in EPC-mediated postischemic kidney protection.
abstract: Renal ischemia induces peritubular capillary rarefication and fibrosis, with the latter partly resulting from the endothelial-to-mesenchymal transition (EndoMT). Endothelial cilia transmit blood flow-associated forces into the cell. Early endothelial progenitor cells (eEPCs) have been shown to protect mice from acute kidney injury in the short term. The aim of the present study was to analyze midterm consequences of eEPC treatment in the context of endothelial cilia and the EndoMT. Male C57/Bl6N mice were subjected to unilateral renal ischemia postuninephrectomy. Syngeneic murine eEPCs were systemically injected at the time of reperfusion. Animals were investigated 1, 4, and 6 wk later. Cultured mature endothelial cells were exposed to a variable flow with versus without eEPC supernatant incubation. Systemically injected eEPCs reduced serum creatinine levels atweek 1(35 and 45 min) andweek 4(45 min). Interstitial fibrosis was significantly diminished by cell treatment at all time points as well. The EndoMT was less pronounced atweek 4(35 min) andweek 6(45 min). eEPC supernatant reduced α-smooth muscle actin expression and α-tubulin abundance in flow-treated cultured mature endothelial cells, and percentages of cilium-positive cells increased. The loss of peritubular capillaries was prevented by eEPCs. Intrarenal endothelial α-tubulin decreased postischemia and was further reduced by eEPC administration. We conclude that eEPCs are capable of reorganizing the endothelial cytoskeleton in an indirect manner, ultimately resulting in stabilization of the endothelial ciliome. The investigation indicates an antimesenchymal role of endothelial cilia in the process of postischemic tissue fibrosis/EndoMT.
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany d.patschan@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Patschan
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schwarze
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Henze
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Patschan
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: G A
authors.initials: GA
authors.lastname: Müller
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D002923:Cilia / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D015427:Reperfusion Injury / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
keywords: acute kidney injury; endothelial cilia; endothelial progenitor cells; endothelial-to-mesenchymal transition