Overexpression of Mafb in podocytes protects against diabetic nephropathy

Naoki Morito, Keigyou Yoh, Masami Ojima, Midori Okamura, Megumi Nakamura, Michito Hamada, Homare Shimohata, Takashi Moriguchi, Kunihiro Yamagata, Satoru Takahashi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We previously showed that the transcription factor Mafb is essential for podocyte differentiation and foot process formation. Podocytes are susceptible to injury in diabetes, and this injury leads to progression of diabetic nephropathy. In this study, we generated transgenic mice that overexpress Mafb in podocytes using the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb in diabetic nephropathy, Mafb transgenic mice were treated with either streptozotocin or saline solution. Diabetic nephropathy was assessed by renal histology and biochemical analyses of urine and serum. Podocyte-specific overexpression of Mafb had no effect on body weight or blood glucose levels in either diabetic or control mice. Notably, albuminuria and changes in BUN levels and renal histology observed in diabetic wild-type animals were ameliorated in diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy through regulation of slit diaphragmproteins, antioxidative enzymes, and Notch pathways in podocytes and suggest that Mafb could be a therapeutic target.

Original languageEnglish
Pages (from-to)2546-2557
Number of pages12
JournalJournal of the American Society of Nephrology
Volume25
Issue number11
DOIs
Publication statusPublished - 2014 Nov 1

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Overexpression of Mafb in podocytes protects against diabetic nephropathy'. Together they form a unique fingerprint.

  • Cite this

    Morito, N., Yoh, K., Ojima, M., Okamura, M., Nakamura, M., Hamada, M., Shimohata, H., Moriguchi, T., Yamagata, K., & Takahashi, S. (2014). Overexpression of Mafb in podocytes protects against diabetic nephropathy. Journal of the American Society of Nephrology, 25(11), 2546-2557. https://doi.org/10.1681/ASN.2013090993