Medical Molecular Morphology

, Volume 47, Issue 4, pp 213–223 | Cite as

Renal atrophy after ischemia–reperfusion injury depends on massive tubular apoptosis induced by TNFα in the later phase

  • Takaomi Adachi
  • Noriyuki Sugiyama
  • Hideo Yagita
  • Takahiko Yokoyama
Original Paper


Recent studies have suggested that acute kidney injury (AKI) develops into chronic kidney disease (CKD). However, a mechanism for disease progression from AKI to CKD has not been established. We developed two ischemia–reperfusion injury (IRI) mouse models, a repaired kidney model and an atrophic kidney model, and studied the mechanisms of renal atrophy after IRI by comparing the two models. We found that renal atrophy after IRI depended on tubular apoptosis at 14 days after IRI. Moreover, we found that Tnfα and FasL mRNA were synchronously expressed at the time of tubular apoptosis. To elucidate the relationship between tubular apoptosis and apoptotic ligands, we administered TNFα and FasL neutralizing antibodies according to the time of tubular apoptosis. TNFα blockade significantly repressed tubular apoptosis, resulting in the prevention of renal atrophy. FasL blockade could not repress tubular apoptosis, resulting in renal atrophy. We also found that TNF receptors were expressed in the kidney at 14 days after IRI, but Fas receptor was not. We concluded that renal atrophy after IRI depends on tubular apoptosis induced by the TNFα signaling pathway in the later phase of renal IRI, and that TNFα blockade could be a potential new therapeutic approach for improving renal prognosis after AKI.


TNFα Apoptosis Atrophy Ischemia–reperfusion injury 



This work was supported by a Grant-in-Aid for Scientific Research (C, 23591197) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest


Supplementary material

795_2013_67_MOESM1_ESM.pdf (2.3 mb)
Supplementary material 1 Fig. 1 Relationship between the duration of ischemia and kidney phenotypes after IRI. a Body weights of each IRI group (sham, 30, 45, 60, and 90 min) at 28 days after IRI (sham, 30, 90 min: n = 3; 45, 60 min: n = 8). The body weights showed no differences by ischemic interval. b Time-course of KW/BW of IRI45 and sham (IRI45: n = 8, sham: n = 3). There was no difference between IRI45 and sham in the time-course of KW/BW. c Histological change at 56 days after IRI45 and IRI60 as estimated by PAS staining (bar 50 μm). d Time-course of serum creatinine in IRI45 and IRI60 (n = 3). Fig. 2 PAS stained section of kidneys in IRI45 and IRI60 at 0, 1, 3, 7, 14, and 28 days after IRI (bar 100 μm) (PDF 2362 kb)


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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2014

Authors and Affiliations

  • Takaomi Adachi
    • 1
    • 2
  • Noriyuki Sugiyama
    • 1
    • 3
  • Hideo Yagita
    • 4
  • Takahiko Yokoyama
    • 1
  1. 1.Department of Anatomy and Developmental Biology, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Division of Nephrology, Department of MedicineKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Division of Life Science, Department of Anatomy and Cell BiologyOsaka Medical CollegeTakatsukiJapan
  4. 4.Department of ImmunologyJuntendo University School of MedicineTokyoJapan

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