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

• DOI: 10.1016/j.kint.2020.02.038
• Publication Date: 2020-04-28T01:28:38Z
• Authors: Toshiaki Usui; Naoki Morito; Hossam H. Shawki; Yoshinori Sato; Hiroyasu Tsukaguchi; Michito Hamada; Hyojung Jeon; Manoj Kumar Yadav; Akihiro Kuno; Yuki Tsunakawa; Risa Okada; Takaaki Ojima; Maho Kanai; Keigo Asano; Yuki Imamura; Ryusuke Koshida; Keigyou Yoh; Joichi Usui; Hideki Yokoi; Masato Kasahara; Ashio Yoshimura; Masafumi Muratani; Takashi Kudo; Hisashi Oishi; Kunihiro Yamagata; Satoru Takahashi
• Keywords: 0301 basic medicine; Mice; Proteinuria; 0303 health sciences; 03 medical and health sciences; Nephrotic Syndrome; Glomerulosclerosis, Focal Segmental; Podocytes; MafB Transcription Factor; Basic Helix-Loop-Helix Transcription Factors; Animals; Humans; Mice, Transgenic

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.