Kidney Week

Abstract: TH-PO027

Upregulation of Matrix Metalloproteinase-10 in Glomerular Cells and Macrophages by Inflammation

Session Information

• Glomerular: Basic/Experimental Immunology and Inflammation - I
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

• 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

• Osaki, Keisuke, Kyoto University Graduate School of Medicine, Kyoto, Japan

Keisuke Osaki,

• Kato, Yukiko, Kyoto University Graduate School of Medicine, Kyoto, Japan

Yukiko Kato,

• Toda, Naohiro, Kyoto University Graduate School of Medicine, Kyoto, Japan

Naohiro Toda,

• Ishii, Akira, Kyoto University Graduate School of Medicine, Kyoto, Japan

Akira Ishii,

• Mori, Keita P., Kyoto University Graduate School of Medicine, Kyoto, Japan

Keita P. Mori,

• Ohno, Shoko, Kyoto University Graduate School of Medicine, Kyoto, Japan

Shoko Ohno,

• Mori, Kiyoshi, School of Pharmaceut Sci, University of Shizuoka, Shizuoka, Japan

Kiyoshi Mori,

• Saleem, Moin, University of Bristol, Bristol, United Kingdom

Moin Saleem,

• Matsusaka, Taiji, Tokai University School of Medicine, Isehara, KANAGAWA, Japan

Taiji Matsusaka,

• Mukoyama, Masashi, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan

Masashi Mukoyama,

• Yanagita, Motoko, Kyoto University Graduate School of Medicine, Kyoto, Japan

Motoko Yanagita,

• Yokoi, Hideki, Kyoto University Graduate School of Medicine, Kyoto, Japan

Hideki Yokoi,

Background

Recently, we and others have unveiled the novel renal function of natriuretic peptide receptor/guanylyl cyclase-A (GC-A) system on antagonizing aldosterone-induced podocyte injury as well as the conventional effects on natriuresis and reducing blood pressure. High salt-fed systemic or podocyte-specific GC-A knockout mice with aldosterone and uninephrectomy showed accelerated glomerular injury with massive albuminuria. However, genes involved in glomerular injury are elusive.

Methods

By using microarray analysis, we compared gene expression in the glomeruli of systemic GC-A knockout mice and wild-type mice with aldosterone and examined gene expression by glomerular cells and macrophages with TNF-α. We performed immunohistochemical study for an identified protein.

Results

We identified matrix metalloproteinase-10 (MMP-10) in glomeruli of aldosterone-induced systemic GC-A KO mice. We confirmed that the expression of MMP-10 from the glomeruli in systemic and podocyte-specific GC-A knockout mice was 50 and 3 times higher than that from control mice by real-time PCR, respectively. Immunostaining revealed that aldosterone–infused systemic or podocyte-specific GC-A knockout mice exhibited a mild increase in MMP-10-positive cells in glomeruli and distal tubular cells. MMP-10 staining of renal biopsy samples in human IgA nephropathy also demonstrated the increase of MMP-10 staining intensity in glomerular cells. In vitro, mRNA expression of MMP-10 was increased in human podocytes as well as murine mesangial cells with TNF-α stimulation. In murine macrophages (RAW264.7 cells), the expression of MMP-10 wasn’t increased with TNF-α alone, but was upregulated when both TNF-α and connective tissue growth factor (CTGF) were given at the same time. Additionally, TGF-β stimulation induced MMP-10 overexpression in podocytes.

Conclusion

These results suggest that glomerular MMP-10 in podocytes, mesangial cells and macrophages is increased in aldosterone-infused GC-A KO mice, and could play a role on inflammation during glomerular injury.