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Kidney Week

Abstract: PO2439

Role of Mast Cells in the Progression of Peritoneal Fibrosis in Rats with Chronic Renal Failure

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Author

  • Kazama, Itsuro, Miyagi University, School of Nursing, Kurokawa-gun, Miyagi, Japan
Background

Mast cells, that are originally derived from hematopoietic stem cells, secrete inflammatory cytokines besides their exocytotic release of chemical mediators. Recent studies also demonstrated that mast cells synthesize fibroblast-activating factors in chronic inflammatory diseases, thereby facilitating the progression of organ fibrosis.

Methods

Using rat models with chronic renal failure (CRF) induced by 5/6 nephrectomy, the histopathological features of CRF rat peritoneum were examined. We also treated the CRF rats with tranilast, a mast cell stabilizer, to reveal the involvement of mast cells in the progression of peritoneal fibrosis.

Results

In fibrotic areas of CRF rat peritoneum, mast cells proliferated in situ and increased their activity by producing fibroblast growth factors. Therapeutic intervention with tranilast, a potent mast cell stabilizer, actually slowed the progression of peritoneal fibrosis. Therefore, the activation of mast cells were considered to be responsible for the progression of peritoneal fibrosis in uremic condition. Additionally, we employed the standard patch-clamp whole-cell recording technique in mast cells to examine the effects of other mast cell stabilizers, since the process of exocytosis in mast cells can continuously be monitored electrophysiologically by the changes in the membrane capacitance (Cm). Second generation anti-histamine drugs, such as olopatadine and loratadine, markedly suppressed the increase in the Cm and directly inhibited the exocytotic process, suggesting their potency as mast cell stabilizers. In additional morphological studies, these drugs actually caused inward bending of mast cell membranes and counteracted the exocytosis-induced cellular surface deformation.

Conclusion

Taken together these in vivo and in vitro evidence, our results strongly indicated the therapeutic efficacy of targeting mast cells to ameliorate organ fibrosis in chronic diseases, besides the treatment of allergic diseases.