Kidney Week

Abstract: FR-PO105

TRPM7 Is a Potential Therapeutic Target in Progressive Renal Disease

Session Information

• Molecular Mechanisms of CKD - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Author

• Suzuki, Sayuri, The Queen''s Medical Center, Honolulu, Hawaii, United States

Sayuri Suzuki,

Background

Unilateral Ureteral Obstruction (UUO) is a representative model of nephritis with progressive tubulointerstitial injury and renal fibrosis occurring by inflammation that is suitable for investigating the cellular and molecular events that occur during progressive renal fibrosis associated with cell proliferation and apoptosis. Blocking tubular epithelial cell proliferation is crucial to preventing the renal tubule dilation and the progression of kidney damage.
TRPM7 belongs to the Transient Receptor Potential Melastatin family of ion channels. Our work shows that TRPM7 is a Ca²⁺- and Mg²⁺-conducting ion channel fused with a functional kinase. TRPM7 plays a key role in a variety of diseases, including malaria invasion, neuronal death in ischemia, cancer and cardiac fibrillation. TRPM7 is aberrantly over-expressed in lung, liver and heart fibrosis. It is also overexpressed after renal ischemia-reperfusion, an event that induces kidney injury and fibrosis. However, the role of TRPM7 is unclear in kidney fibrosis.

Methods

We created UUO mouse model, compared the expression level of TRPM7 in UUO kidneys and control kidneys at Day7 using qRT-PCR, western blotting assay and immunohistochemistry. Our lab’s drug screening efforts have identified waixenicin A that is the currently only specific and potent TRPM7 inhibitor. Using NRK49F and NRK52E cells, we investigated the inhibitory efficacy of waixenicin A on MTT cell growth assay.

Results

The expression levels of TRPM7 mRNA and protein in UUO kidneys were higher than control kidneys, TRPM7 particularly increased on tubular epithelial cells. The TRPM7 positive cell number increased twice on both of renal tubular epithelial cells and tubulointerstitial cells in UUO kidneys compared to control kidneys. Waixenicin A inhibited the cell growth of renal epithelial cells and fibroblasts in vitro.

Conclusion

TRPM7 up-regulated in progressing inflammatory renal damage, waixenicin A could be capable of inhibiting kidney cell proliferation and fibrosis in renal disease.

Funding

• Private Foundation Support