Cadherin-9 is a novel cell surface marker for the heterogeneous pool of renal fibroblasts.
BACKGROUND
Interstitial fibroblasts are a minor, but nevertheless very important, component of the kidney. They secrete and 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.


RESULTS
The expression of cadherin-9 in various human renal cell lines and tissues was studied on the mRNA level by RT-PCR and on the protein level with the help of newly generated cadherin-9 antibodies. The classical type II cadherin-9, so far only described in the neural system, was identified as a reliable surface marker for renal fibroblasts. Compared to FSP1, a widely-used cytosolic renal fibroblast marker, cadherin-9 showed a more restricted expression pattern in human kidney. Under pathological conditions, cadherin-9 was expressed in the stroma of renal cell carcinoma, but not in the tumor cells themselves, and in renal fibrosis the percentage 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 cell interactions.


CONCLUSIONS
Cadherin-9 represents a novel and reliable cell surface marker for fibroblasts in healthy and diseased kidneys. Together with the established marker molecules FSP1, CD45 and alpha smooth muscle actin, cadherin-9 can now be used to differentiate the heterogenic pool of renal fibroblasts into resident and activated fibroblasts, immigrated bone marrow derived fibroblast precursors and cells in different stages of epithelial mesenchymal transition.
Section for Transplantation Immunology and Immunohematology, Center for Medical Research, University Medical Clinic, Tübingen, Germany.
Cornelia
C
Thedieck
Hubert
H
Kalbacher
Markus
M
Kuczyk
Gerhard A
GA
Müller
Claudia A
CA
Müller
Gerd
G
Klein
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000473:pathology; D018929:Cell Culture Techniques; D002460:Cell Line; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D007680:Kidney Neoplasms / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4
D015415:Biomarkers; C430712:CDH9 protein, human; D015820:Cadherins; D002135:Calcium-Binding Proteins; D007381:Intermediate Filament Proteins; D000071999:S100 Calcium-Binding Protein A4; C077591:S100A4 protein, human