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Implication of CD38 Gene in Podocytes Epithelial to Mesenchymal Transition and Glomerular Sclerosis
Author(s) -
Boini Krishna M,
Xia Min,
Li PinLan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.665.12
Subject(s) - epithelial–mesenchymal transition , multiple sclerosis , podocyte , glomerulosclerosis , mesenchymal stem cell , gene , transition (genetics) , cd38 , cancer research , medicine , microbiology and biotechnology , pathology , biology , genetics , immunology , kidney , stem cell , proteinuria , cd34
CD38 is a multifunctional protein involving in a number of signaling pathways. Given that the lack of CD38 is considered as a dedifferentiation marker of lymphocytes and other cells, we hypothesized that CD38 and its signaling pathway may participate in the epithelial‐to‐mesenchymal transition (EMT) process of podocytes and thereby leads to glomerular injury or sclerosis. CD38 gene targeted mice and their wild type littermates were used to test this hypothesis. It was found that the CD38 expression as measured by real time PCR, Western blotting and its enzyme activity, namely, cADPR production and conversion of cGDPR were significantly lower in CD38 −/− mice compared to CD38 +/+ littermates. Morphological examinations showed profound injury in the glomeruli from CD38 −/− mice as compared to CD38 +/+ mice (the glomerular damage index (GDI) of 1.51 ± 0.12 in CD38 −/− mice vs. 1.05 ± 0.03 in CD38 +/+ mice). This enhanced glomerular injury in CD38 −/− mice was accompanied by increased albuminuria. Fluorescent Immunohistochemical analyses also illustrated podocyte damages in the glomeruli from CD38 −/− mice, as shown by decreased expression of podocin and enhanced expression of desmin. Moreover, RT‐PCR and fluorescent confocal microscopy demonstrated increased expression of mesenchymal markers (FSP‐1 and α‐SMA) and reduced expression of epithelial markers (P‐Cadherin and Zo‐1) in the glomeruli from CD38 −/− mice compared to CD38 +/+ mice. In conclusion, our observations reveal that the normal expression of CD38 importantly contributes to the regulation of EMT of podocytes and that defect of this gene expression may be a critical mechanism inducing EMT and consequently resulting in glomerular sclerosis (supported by NIH grants HL‐091464, HL‐75316 and DK54927).