Cadherin-9 Is a Novel Cell Surface Marker for the Heterogeneous Pool of Renal Fibroblasts 英文参考文献.docVIP

Cadherin-9IsaNovelCellSurfaceMarkerforthe HeterogeneousPoolofRenalFibroblasts CorneliaThedieck1,HubertKalbacher2,MarkusKuczyk3,GerhardA.Mu¨ller4,ClaudiaA.Mu¨ller1,GerdKlein1* 1Section for Transplantation Immunology and Immunohematology, Center for Medical Research, University Medical Clinic, Tu¨bingen, Germany, 2Medical and Natural Sciences Research Centre, University of Tu¨bingen, Tu¨bingen, Germany, 3Department of Urology, University Medical Clinic, Tu¨bingen,Germany,4DepartmentofNephrologyandRheumatology,Georg-August-UniversityMedicalCenter,Go¨ttingen,Germany Background.Interstitialfibroblastsareaminor,butneverthelessveryimportant,componentofthekidney.Theysecreteand remodel extracellular matrix and they produce active compounds such as erythropoietin. However, studying human renal fibroblasts has been hampered by the lack of appropriate surface markers. Methods and Findings. The expression of cadherin-9invarioushumanrenalcelllinesandtissueswasstudiedonthemRNAlevelbyRT-PCRandontheproteinlevelwith thehelpofnewlygeneratedcadherin-9antibodies.TheclassicaltypeIIcadherin-9,sofaronlydescribedintheneuralsystem, was identified as a reliable surface marker for renal fibroblasts. Compared to FSP1, a widely-used cytosolic renal fibroblast marker,cadherin-9showedamorerestrictedexpressionpatterninhumankidney.Underpathologicalconditions,cadherin-9 wasexpressedinthestromaofrenalcellcarcinoma,butnotinthetumorcellsthemselves,andinrenalfibrosisthepercentage of cadherin-9-positive cells was clearly elevated 3 to 5 times compared to healthy kidney tissue. Induction of epithelial mesenchymal transition in renal epithelial cells with cyclosporin-A, which causes renal fibrosis as a side effect, induced cadherin-9 expression. Functional studies following siRNA-mediated knockdown of cadherin-9 revealed that it acts in the kidney like a typical classical cadherin. It was found to be associated with catenins and to mediate homophilic but not heterophilic cellinteractions.Conclusions.Cadhe