Cadherin-9 Is a Novel Cell Surface Marker for the Heterogeneous Pool of Renal Fibroblasts

Abstract

BackgroundInterstitial 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.Methods and FindingsThe 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.ConclusionsCadherin-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 α 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.

Sp1-mediated microRNA-182 expression regulates lung cancer progression

“…Given that ADAM9 is also involved in the activation of the Wnt pathway, Sp1 and miR-182 might connect the Kras and the Wnt pathway. In addition, CDH9 also involves in the cancer metastasis [48]. …”

Characterization of Epstein–Barr virus (EBV) BZLF1 gene promoter variants and comparison of cellular gene expression profiles in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV‐associated hemophagocytic lymphohistiocytosis

“…Thus, RIPK2‐activated apoptosis and autophagy may be responsible for pathogenesis of chronic active EBV infection. However, it remains unknown why the CDH9 gene was upregulated in chronic active EBV infection, because CDH9 is expressed normally in the human brain and kidney [Shimoyama et al, 2000; Thedieck et al, 2007].…”

The renal cortical interstitium: morphological and functional aspects

“…S100A4/FSP1 also labels smooth muscle cells of arterioles (Le Hir et al 2005 ) and metastasing cells (Davies et al 1993 ; Gibbs et al 1994 ; Mazzucchelli 2002 ; Garrett et al 2006 ). Recently the stromal cadherin 9 (Thedieck et al 2007 ) has been proposed as surface marker for fibroblasts in the human kidney. Cadherin 9 is expressed in a very small population of interstitial cells in healthy kidneys.…”

“…In the diseased kidney the incidence of labeled cells is higher. Cadherin 9 partially co-localizes with cells labeled by FSP1/S100A4 and with mononuclear cells (Thedieck et al 2007 ).…”