Journal of Nephrology

, Volume 29, Issue 1, pp 53–62 | Cite as

Role of tubulointerstitial plasmin in the progression of IgA nephropathy

  • Takahiro UchidaEmail author
  • Takashi Oda
  • Hanako Takechi
  • Hidehito Matsubara
  • Atsushi Watanabe
  • Kojiro Yamamoto
  • Naoki Oshima
  • Yutaka Sakurai
  • Takako Kono
  • Hideyuki Shimazaki
  • Seiichi Tamai
  • Hiroo Kumagai
Original Article



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


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.


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.


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.


Epithelial-to-mesenchymal transition Fibrosis IgA nephropathy Plasmin 



We thank our colleague Ms. Toshie Fujiwara for expert secretarial assistance.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

The study protocols were approved by the Ethical Committee of National Defense Medical College.

Informed consent

Informed consent was obtained from each participating patient in accordance with the principles of the Declaration of Helsinki.


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Copyright information

© Italian Society of Nephrology 2015

Authors and Affiliations

  • Takahiro Uchida
    • 1
    Email author
  • Takashi Oda
    • 2
  • Hanako Takechi
    • 1
  • Hidehito Matsubara
    • 1
  • Atsushi Watanabe
    • 1
  • Kojiro Yamamoto
    • 1
  • Naoki Oshima
    • 1
  • Yutaka Sakurai
    • 3
  • Takako Kono
    • 4
  • Hideyuki Shimazaki
    • 4
  • Seiichi Tamai
    • 4
  • Hiroo Kumagai
    • 1
  1. 1.Department of Nephrology and EndocrinologyNational Defense Medical CollegeTokorozawaJapan
  2. 2.Department of NephrologyTokyo Medical University Hachioji Medical CenterHachiojiJapan
  3. 3.Department of Preventive Medicine and Public HealthNational Defense Medical CollegeTokorozawaJapan
  4. 4.Department of Laboratory MedicineNational Defense Medical CollegeTokorozawaJapan

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