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01.02.2016 | Original Article

Role of tubulointerstitial plasmin in the progression of IgA nephropathy

verfasst von: Takahiro Uchida, Takashi Oda, Hanako Takechi, Hidehito Matsubara, Atsushi Watanabe, Kojiro Yamamoto, Naoki Oshima, Yutaka Sakurai, Takako Kono, Hideyuki Shimazaki, Seiichi Tamai, Hiroo Kumagai

Erschienen in: Journal of Nephrology | Ausgabe 1/2016

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Abstract

Background

Plasmin has recently been reported to be associated with renal fibrosis in experimental models, but its role in human renal diseases is unclear.

Methods

Fifty-seven patients with IgA nephropathy (IgAN) were evaluated retrospectively. Plasmin in their renal biopsy tissues was assessed by in situ zymography using a plasmin-sensitive synthetic peptide, and the relationships between patients’ histologic or clinical parameters and their renal plasmin activity [assessed semiquantitatively by calculating the positively stained percentage of the total tubulointerstitial (TI) area] were evaluated.

Results

Plasmin activity was observed almost exclusively in the TI space (mainly in the interstitium and partly in the tubular epithelial cells) and was significantly stronger in patients with TI lesion (tubular atrophy/interstitial fibrosis and tubulointerstitial inflammation) than in those without TI lesion. It was significantly and positively correlated with the global glomerulosclerosis rate and significantly and negatively correlated with estimated glomerular filtration rate not only at the time of renal biopsy but also at the end of the follow-up period. Double stainings for plasmin activity and inflammatory cells, cytokeratin, or α-smooth muscle actin (α-SMA) in selected patients revealed TI infiltration of inflammatory cells, attenuated tubular epithelial expression of cytokeratin, and augmented interstitial expression of α-SMA close to upregulated plasmin activity in the TI space.

Conclusions

These data suggest that TI plasmin is associated with TI inflammation leading to renal fibrosis, and can cause the decline in renal function seen in patients with IgAN. Reducing plasmin in situ may therefore be a promising therapeutic approach slowing renal fibrogenesis and improving renal function.

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Titel: Role of tubulointerstitial plasmin in the progression of IgA nephropathy
verfasst von: Takahiro Uchida
Takashi Oda
Hanako Takechi
Hidehito Matsubara
Atsushi Watanabe
Kojiro Yamamoto
Naoki Oshima
Yutaka Sakurai
Takako Kono
Hideyuki Shimazaki
Seiichi Tamai
Hiroo Kumagai
Publikationsdatum: 01.02.2016
Verlag: Springer International Publishing
Erschienen in: Journal of Nephrology / Ausgabe 1/2016
Print ISSN: 1121-8428
Elektronische ISSN: 1724-6059
DOI: https://doi.org/10.1007/s40620-015-0205-1

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Role of tubulointerstitial plasmin in the progression of IgA nephropathy