Kidney Week

Abstract: TH-PO992

Transcription Factor MAFB is a New Key Regulator of Podocyte Autophagy

Session Information

• Pathology and Lab Medicine: Basic
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1501 Pathology and Lab Medicine: Basic

Authors

• Yamahara, Kosuke, Shiga University of Medical Science, Otsu, Shiga, Japan

Kosuke Yamahara,

• Bork, Tillmann, University Hospital Freiburg, Freiburg, Germany

Tillmann Bork,

• Liang, Wei, Renmin Hospital of Wuhan University, Wuhan, China

Wei Liang,

• Schell, Christoph, University Hospital Freiburg, Freiburg, Germany

Christoph Schell,

• Kume, Shinji, Shiga University of Medical Science, Otsu, Shiga, Japan

Shinji Kume,

• Yoshibayashi, Mamoru, Shiga University of Medical Science, Otsu, Shiga, Japan

Mamoru Yoshibayashi,

• Araki, Shin-ichi, Shiga University of Medical Science, Otsu, Shiga, Japan

Shin-ichi Araki,

• Maegawa, Hiroshi, Shiga University of Medical Science, Otsu, Shiga, Japan

Hiroshi Maegawa,

• Huber, Tobias B., University Medical Center Hamburg, Hamburg, Germany

Tobias B. Huber,

Background

Autophagy is an intracellular catabolic system with protective roles against fasting and cellular damage. Podocytes have high autophagy activity in basal condition; however, their autophagy regulating mechanisms are unclear. To reveal the regulating mechanism of podocyte autophagy, we focused on transcriptional regulation of autophagy related genes.

Methods

We searched the candidate transcription factors which regulate autophagy related genes with the potential to bind to transcription regulatory sites from the web database Motifmap. Next, we sorted the transcription factors which are strongly expressed in podocytes from RNA sequence data of primary culture podocytes. MAFB was extracted as a candidate from the results of these two analyses. To investigate the location of MAFB in the cell, we stained MAFB protein in mouse kidney sections and human podocyte cell lines. To exhibit the transcriptional role of MAFB on autophagy activation, we modified MAFB expression levels in human podocyte cell lines using either overexpression vector or siRNA, and evaluated autophagy activity by LC3-II protein expression. In addition, to reveal the role of MAFB for cell damage, we induced cell damage by incubation with palmitate and evaluated apoptosis and autophagy-related proteins using the cell line of tetracycline-induced overexpression/shRNA of MAFB.

Results

MAFB was localized at nuclear areas in podocytes of mouse kidney sections and human podocyte cell lines. LC3-II protein abundance was significantly increased in the MAFB overexpression group and decreased in siRNA of MAFB group. In cell damage experiments with palmitate, we observed suppression of apoptosis accompanied by high LC3-II protein abundance in the MAFB overexpression group. Phosphorylation of ULK1 proteins, which are well known as a key autophagy regulator, was not significantly changed in any experiment.

Conclusion

We identified the transcription factor MAFB as a novel autophagy regulator independent of phosphorylation of ULK1 in podocytes. The activation of MAFB can be a potential therapeutic target against podocyte damages via autophagy activation.

Funding

• Government Support - Non-U.S.