Abstract: PO1720
Increased Old Astrocyte Specifically Induced Substance (OASIS) in Podocytes Leads to the Progression of Nephrotic Syndrome
Session Information
- Podocyte Pathobiology: Basic Science Studies and Animal Models
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Miyake, Yoshiaki, Osaka Daigaku, Suita, Osaka, Japan
- Obana, Masanori, Osaka Daigaku, Suita, Osaka, Japan
- Yamamoto, Ayaha, Osaka Daigaku, Suita, Osaka, Japan
- Noda, Shunsuke, Osaka Daigaku, Suita, Osaka, Japan
- Tanaka, Koki, Osaka Daigaku, Suita, Osaka, Japan
- Tanaka, Shota, Osaka Daigaku, Suita, Osaka, Japan
- Maeda, Makiko, Osaka Daigaku, Suita, Osaka, Japan
- Asanuma, Katsuhiko, Chiba Daigaku Daigakuin Igaku Kenkyuin Igakubu, Chiba, Chiba, Japan
- Fujio, Yasushi, Osaka Daigaku, Suita, Osaka, Japan
Background
Old astrocyte specifically induced substance (OASIS) is a transcription factor of the CREB/ATF family. Previously, we found that OASIS was expressed in podocytes in murine kidneys. However, the pathophysiological roles of OASIS in podocytes remain unclear. The aim of this study is to elucidate the role of OASIS in podocytes.
Methods
To assess the relevance of OASIS to renal pathology, the expression of OASIS in glomeruli of lipopolysaccharide (LPS)-treated mice or streptozotocin (STZ)-treated diabetic mice was examined by laser capture microdissection, followed by immunoblotting. To further investigate the functional roles of OASIS in podocytes, podocyte-restricted OASIS overexpressing transgenic (OASIS TG) mice were established. Urinary albumin-creatinine ratio (uACR) was measured. Podocyte injury was assessed by electron microscopy. Tubular injury was evaluated by PAS staining and by measuring LCN2 mRNA expression. Masson’s trichrome staining and quantitative PCR for fibrosis-related genes, COL1A1 and FN1, were performed to analyze tubulointerstitial fibrosis. To explore the effect of OASIS on podocyte actin cytoskeleton in vitro, phalloidin staining was performed on lentivirus-induced OASIS overexpressing murine cultured podocytes.
Results
OASIS expression was increased in glomeruli of both LPS-treated and diabetic mice. uACR was significantly increased in OASIS TG mice (uACR (µg/mg): control; 35.1±24.9, OASIS TG; 8930.0±8461.4, n=9 for control, n=7 for OASIS TG), and electron microscope analysis showed that OASIS overexpression in podocytes caused foot process effacement. In addition, damaged tubules and LCN2 upregulation were observed in OASIS TG mice. Furthermore, Masson’s trichrome staining showed that OASIS overexpression in podocytes evoked kidney fibrosis, and the expression of COL1A1 and FN1 were upregulated in OASIS TG mice. Consistent with in vivo study, OASIS overexpressing podocytes showed the reduction in actin stress fiber formation.
Conclusion
The increased OASIS in podocytes contributes to nephrotic progression.