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Kidney Week

Abstract: TH-OR007

C-Type Lectin Mincle Accelerates Renal Ischemia-Reperfusion Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Tanaka, Miyako, Nagoya University, Nagoya, Japan
  • Saka-Tanaka, Marie, Nagoya University, Nagoya, Japan
  • Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Suganami, Takayoshi, Nagoya University, Nagoya, Japan
Background

Evidence has accumulated suggesting that pathogen sensors such as Toll-like receptors contribute to the pathogenesis of various non-infectious diseases. It is also known that Macrophage-inducible C-type lectin (Mincle), a pathogen sensor for Mycobacterium tuberculosis, can sense cell death, suggesting the role of Mincle in sterile inflammation. Indeed, we recently demonstrated that Mincle plays an important role in obesity-induced adipose tissue inflammation, thereby regulating systemic insulin resistance. In this study, we investigated the pathophysiologic role of Mincle in a mouse model of acute kidney injury.

Methods

Eight to eleven week-old male Mincle-deficient mice or wildtype mice were subjected to ischemia-reperfusion injury. After 30 minutes of ischemic period, the clamp of left kidney was released to induce reperfusion. The right side of kidney was resected at this time point.

Results

There was a marked upregulation of Mincle mRNA in the injured kidney from 6 hours after the reperfusion. Histological and flow cytometric analysis revealed that most of the Mincle-expressing cells were proinflammatory M1 macrophages infiltrating toward the damaged tubules. All of the Mincle-deficient mice were alive during the experimental period, while about half of wildtype mice died due to renal failure. Consistently, serum concentrations of BUN and creatinine along with mRNA expression of proinflammatory cytokines were significantly ameliorated in the kidney of Mincle-deficient mice compared to wildtype mice. Moreover, wildtype mice were protected against ischemia-reperfusion injury when they received bone marrow transplantation from Mincle-deficient mice.

Conclusion

This study indicates that Mincle in macrophages plays an important role in the pathogenesis of acute kidney injury. Our data also suggest that Mincle senses damaged tubular epithelial cells to accelerate inflammation.

Funding

  • Government Support - Non-U.S.