2. Academic Validation
  3. Upregulation of OASIS/CREB3L1 in podocytes contributes to the disturbance of kidney homeostasis

Upregulation of OASIS/CREB3L1 in podocytes contributes to the disturbance of kidney homeostasis

  • Commun Biol. 2022 Jul 22;5(1):734. doi: 10.1038/s42003-022-03709-x.
Yoshiaki Miyake  # 1,  Masanori Obana  # 2 3 4 5,  Ayaha Yamamoto  # 1,  Shunsuke Noda 1,  Koki Tanaka 1,  Hibiki Sakai 1,  Narihito Tatsumoto 6,  Chihiro Makino 6,  Soshi Kanemoto 7,  Go Shioi 8,  Shota Tanaka 1,  Makiko Maeda 9 10,  Yoshiaki Okada 1,  Kazunori Imaizumi 7,  Katsuhiko Asanuma 6,  Yasushi Fujio 1 11
Affiliations

Affiliations

  • 1 Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
  • 2 Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan. obana@phs.osaka-u.ac.jp.
  • 3 Radioisotope Research Center, Institute for Radiation Sciences, Osaka University, Osaka, Japan. obana@phs.osaka-u.ac.jp.
  • 4 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan. obana@phs.osaka-u.ac.jp.
  • 5 Global Center for Medical Engineering and Informatics (MEI), Osaka University, Osaka, Japan. obana@phs.osaka-u.ac.jp.
  • 6 Department of Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • 7 Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
  • 8 Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • 9 Laboratory of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
  • 10 Medical Center for Translational Research, Department of Medical Innovation, Osaka University Hospital, Osaka, Japan.
  • 11 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
  • # Contributed equally.
PMID: 35869269 DOI: 10.1038/s42003-022-03709-x
Abstract

Podocyte injury is involved in the onset and progression of various kidney diseases. We previously demonstrated that the transcription factor, old astrocyte specifically induced substance (OASIS) in myofibroblasts, contributes to kidney fibrosis, as a novel role of OASIS in the kidneys. Importantly, we found that OASIS is also expressed in podocytes; however, the pathophysiological significance of OASIS in podocytes remains unknown. Upon lipopolysaccharide (LPS) treatment, there is an increase in OASIS in murine podocytes. Enhanced serum creatinine levels and tubular injury, but not albuminuria and podocyte injury, are attenuated upon podocyte-restricted OASIS knockout in LPS-treated mice, as well as diabetic mice. The protective effects of podocyte-specific OASIS deficiency on tubular injury are mediated by protein kinase C iota (PRKCI/PKCι), which is negatively regulated by OASIS in podocytes. Furthermore, podocyte-restricted OASIS transgenic mice show tubular injury and tubulointerstitial fibrosis, with severe albuminuria and podocyte degeneration. Finally, there is an increase in OASIS-positive podocytes in the glomeruli of patients with minimal change nephrotic syndrome and diabetic nephropathy. Taken together, OASIS in podocytes contributes to podocyte and/or tubular injury, in part through decreased PRKCI. The induction of OASIS in podocytes is a critical event for the disturbance of kidney homeostasis.

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