Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis

• Published in: Kidney international Vol. 98; no. 2; pp. 391 - 403
• Main Authors: Usui, Toshiaki, Morito, Naoki, Shawki, Hossam H., Sato, Yoshinori, Tsukaguchi, Hiroyasu, Hamada, Michito, Jeon, Hyojung, Yadav, Manoj Kumar, Kuno, Akihiro, Tsunakawa, Yuki, Okada, Risa, Ojima, Takaaki, Kanai, Maho, Asano, Keigo, Imamura, Yuki, Koshida, Ryusuke, Yoh, Keigyou, Usui, Joichi, Yokoi, Hideki, Kasahara, Masato, Yoshimura, Ashio, Muratani, Masafumi, Kudo, Takashi, Oishi, Hisashi, Yamagata, Kunihiro, Takahashi, Satoru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2020
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors; focal segmental glomerulosclerosis; Glomerulosclerosis, Focal Segmental - genetics; Humans; MafB; MafB Transcription Factor - genetics; Mice; Mice, Transgenic; Nephrotic Syndrome - genetics; podocyte; Podocytes; Proteinuria - genetics; Proteinuria - prevention & control; transcription factor; transcription factor; MafB; focal segmental glomerulosclerosis; podocyte
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1016/j.kint.2020.02.038

Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid-resistant nephrotic syndrome. Spontaneous remission of FSGS is rare and steroid-resistant FSGS frequently progresses to renal failure. Many inheritable forms of FSGS have been described, caused by mutations in proteins that are important for podocyte function. Here, we show that a basic leucine zipper transcription factor, MafB, protects against FSGS. MAFB expression was found to be decreased in the podocytes of patients with FSGS. Moreover, conditional podocyte-specific MafB-knockout mice developed FSGS with massive proteinuria accompanied by depletion of the slit diaphragm-related proteins (Nphs1 and Magi2), and the podocyte-specific transcription factor Tcf21. These findings indicate that MafB plays a crucial role in the pathogenesis of FSGS. Consistent with this, adriamycin-induced FSGS and attendant proteinuria were ameliorated by MafB overexpression in the podocytes of MafB podocyte-specific transgenic mice. Thus, MafB could be a new therapeutic target for FSGS. [Display omitted]