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Abstract: FR-PO151

MicroRNA-34a Induces Renal Aging by Regulating SIRT1/p53/p21 Pathway and Promoting the Expression of Senescence-Associated Secretory Phenotype (SASP)

Session Information

Category: Geriatric Nephrology

  • 1100 Geriatric Nephrology

Authors

  • Gao, Fanfan, First Affiliated Hospital of Medicine School, Xi’an Jiaotong University, Xi'an, SHaanxi, China
  • Jiang, Hongli, First Affiliated Hospital of Medicine School, Xi?an Jiaotong University, Xi?an, China

Group or Team Name

  • Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
Background

An increasing number of investigations suggest that small non-coding microRNAs play an important role in the regulation of genes involved in various kidney disease. MicroRNA-34a (miR-34a) has been recently implicated in cardiac, endothelial, endothelial progenitor cell, vascular smooth muscle cell senescence, however, its contribution to the aging process of kidney has not been explored so far. The aim of the present study was to analyze miRNA expression profiles and the rule of miR-34a in mice kidney during the aging process.

Methods

The kidneys of male C57BL/6 mice at different ages (3 months, 12 months and 24 months, n=5 per group) were used. Total RNA was extracted using Trizol reagent following the manufacturer's procedure. The total RNA quantity and purity were analysis of Bioanalyzer 2100 with RIN number >7.0. Approximately 1 ug of total RNA were used to prepare small RNA library according to protocol of TruSeq Small RNA Sample Prep Kits. And then we performed the single-end sequencing (36bp or 50bp ) on an Illumina Hiseq 2500 at the LC-BIO following the vendor's recommended protocol. In addition, the results were assessed by real-time PCR and western blotting in kidneys of mice.

Results

Several up- and downregulated miRNAs were identified in the mice kidneys at 3 different ages. We observed the upregulation of miR-26a, miR-214, miR-34a, miR-34c, miR-29c, miR-199a, miR-21a, miR-27a, miR-195a and miR-23a, whereas miR-335, miR-200b, miR-378a, miR-151, miR-486a, miR-615, miR-378 were downregulated in the aging mice kidneys. We found that miR-34a was highly expressed in kidneys isolated from old mice. Moreover, its well-known target, the longevity-associated protein SIRT1, was significantly downregulated during aging in both kidney tissue and HK-2 cells. miR-34a overexpression in HK-2 cells caused cell cycle arrest along with enhanced p21 and p53 protein levels and reduced SIRT1 protein expression. Furthermore, miR-34a ectopic expression induced the expression of SASP, including TNF-α, IL-1α, IL-6, plasminogen activator inhibitor-1 and monocyte chemoattractant protein-1.

Conclusion

In conclusion, our findings suggest that aging-associated increase of miR-34a expression plays an important role in renal aging by inhibition of SIRT1 and activation of p53/p21 pathway as well as the induction of SASP.

Funding

  • Government Support - Non-U.S.