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Enhanced dedifferentiation and injury in mouse podocytes lacking CD38 gene (691.4)
Author(s) -
Boini Krishna,
Xia Min,
Abais Justine,
Li Guangbi,
Li PinLan
Publication year - 2014
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.28.1_supplement.691.4
Subject(s) - synaptopodin , podocyte , cd38 , cd19 , podocalyxin , desmin , biology , medicine , endocrinology , microbiology and biotechnology , chemistry , cancer research , immunohistochemistry , vimentin , immunology , flow cytometry , kidney , stem cell , cd34 , proteinuria
The absence of CD38 in lymphocytes has been used as a dedifferentiation or low differentiation marker for diagnosis of leukemia. Our recent studies have reported that CD38 deficiency leads to phenotypic plasticity of arterial smooth muscle cells. In the present study, we hypothesized that CD38 and its signaling pathway may participate in the regulation of podocyte differentiation and proliferation and its gene defect or dysfunction may lead to podocyte injury and glomerular sclerosis. CD38 gene targeted mice and their wild type littermates were used to test this hypothesis. Western blot, confocal and RT‐PCR analysis demonstrated that synaptopodin (a marker of differentiation) expression was significantly lower in CD38‐/‐ mice compared to CD38+/+ littermates. In contrast, the proliferation marker cyclin E was significantly higher in CD38‐/‐ mice compared to CD38+/+ littermates. Functional studies showed that the urinary albumin and protein excretion were significantly higher in CD38‐/‐ mice than in CD38+/+ mice. 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. Visfatin treatment further decreased the expression of synaptopodin and increased the abundance of cyclin E, which were accompanied by more increased glomerular damage in CD38‐/‐ than in CD38+/+ mice. In vitro studies showed that inhibition of CD38 enhances the synaptopodin expression, but decreases the level of cyclin E in podocytes. In conclusion, our observations reveal that the normal expression of CD38 importantly contributes to the regulation of podocyte proliferation and dedifferentiation and that defect of this gene may be a critical mechanism resulting in podocyte injury and glomerular sclerosis. Grant Funding Source : supported by NIH grants DK54927 and HL‐75316