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Abstract: FR-PO362

Identification of Novel Noninvasive Biomarkers for Cadmium-Induced Renal Injury Through Transcriptome Profiling and Machine Learning

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Feng, Xuefang, Tongji University, Shanghai, Shanghai, China
  • Jin, Xian, EnnovaBio Pharmaceuticals, Shanghai, China
  • Zhou, Rong, Tongji University, Shanghai, Shanghai, China
  • Jiang, Lei, EnnovaBio Pharmaceuticals, Shanghai, China
  • Shou, Jianyong, EnnovaBio Pharmaceuticals, Shanghai, China

Group or Team Name

  • Dept of Nephrology, Yangpu Hospital, School of Medicine, Tongji University.
Background

Kidney is the major toxic organ for cadmium. Once entering the body, cadmium accumulates in proximal tubule cells, resulting in the death of renal epithelial cells through necrotic or apoptotic mechanisms. Of particular interest, cadmium is closely associated with diabetes and the diabetic population is more sensitive to cadmium induced cell damage. The molecular mechanisms underlying the chronic cadmium induced toxicity and the increased susceptibly under diabetic conditions are not fully understood.

Methods

In the present study, we optimized an animal model to study chronic cadmium exposure-induced renal injury by using low dose and repetitive CdCl2 treatment. In conjunction with clinical biochemistry and histopathology, we performed whole transcriptome profiling analyses on kidney. Machine learning with cloud computing was applied to identify novel biomarkers indicative of increased susceptibility in diabetic populations with particular focus on secreted molecules.

Results

Repetitive CdCl2 exposure resulted in cadmium accumulation and remarkable renal injuries with the ob/ob mice manifesting increased severity of renal injury. RNA-Seq data showed that cadmium treatment induced dramatic gene expression changes correlated with the level of cadmium-induced nephrotoxicity. In order to better understand the increases susceptibility under diabetic conditions, we focused our analyses on the low dose ob/ob group. Canonical pathway enrichment analysis revealed key pathways such as Integrin, AP1, IL23, FRA , P53 and TAP63 pathways. Furthermore, a subset of 14 secreted molecules was found to be enriched including Il12b, Ccl2, Il1rn, Gdf15 and Il17f.

Conclusion

A subset of potential sensitive biomarkers which can be measured in peripheral for early diagnosis of cadmium-induced renal injury has been identified. Applicability of these biomarkers in clinical will be tested in human samples.

Funding

  • Government Support – Non-U.S.