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Expression of nephrin, a podocyte specific protein, depends on MafB and ligands of nuclear receptors.
Author(s) -
Motojima Masaru,
Kinomura Masaru,
Matsusaka Taiji,
Ichikawa Iekuni
Publication year - 2015
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.29.1_supplement.880.7
Subject(s) - podocyte , nephrin , transcription factor , biology , microbiology and biotechnology , transfection , cell culture , gene , kidney , genetics , proteinuria
Podocytes are highly differentiated cells within glomeruli and podocyte loss underlies glomerular sclerosis. We analyzed an open database of gene expressions in the kidney, GUDMAP, and found that 18 transcription factors showed podocyte specific expressions. Expressions of 7/18 transcription factors were down‐regulated in a podocyte cell line we developed that do not express nephrin, a podocyte‐specific protein. To identify factor(s) required for podocyte nephrin expression, we generated expression vectors for each of the 7 transcription factors and a reporter vector that expresses EGFP under the control of a mouse nephrin promoter. We then transfected these vectors into the podocyte cell line, but were unable to detect EGFP. However, treatment of transfected podocytes with retinoic acid, glucocorticoid, and vitamin D3 (RGV), induced EGFP expression while RGV alone did not. EGFP induction was not detectable for 48 hour after transfection and treatment indicating that the 7 factors and unknown factor(s) induced by RGV are required for activation of the nephrin promoter. Further analysis revealed that of the 7 factors, MafB, a transcription factor reported to control podocyte development, is crucial in inducing EGFP expression. Thus, MafB together with unknown factor(s) induced by RGV (plus MafB) cooperate in induction of EGFP expression. Comparison of gene expression profiles of EGFP+ podocytes and control cells revealed involvement of Notch signal, Wnt signal as well as epigenetic factors in the remarkable induction of nephrin.