Abstract: PO1362
Expression of miRNA from Urinary Extracellular Vesicles in Patients with Gitelman Syndrome
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - II
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Sung, Chih-Chien, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Lin, Shih-Hua, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Background
Gitelman syndrome (GS) is an inheritable renal tubule disorder with defect of sodium chloride cotransporter on distal convoluted tubule, resulting salt-losing, hypokalemia, hypomagnesemia and hypocalciuria. miRNA plays an important role in renal development and physical regulation. However, the miRNA expression from urinary extracellular vesicles (uEVs) in patients with Gitelman syndrome remains unclear.
Methods
miRNA profiling was conducted in uEVs obtained from 20 genetically confirmed GS patients and 20 healthy controls using small RNA sequencing.
Results
Principal component analysis revealed distinct miRNA expression pattern in GS patients (4 groups) compared with healthy controls (4 groups). The biological process from identified miRNA in uEVs included signaling transduction (24.3%), cell communication (22.6%), regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism (18.4%), and transporter (7.7%). Comparing with healthy controls, differential expression of miRNA showed 18 upregulated miRNA (including has-miR-6825-5p, has-miR-4302, has-miR-4458) and 23 downregulated miRNAs (including has-miR-4740-5p, has-miR-4783-5p, has-miR-4508) in GS patients. Biological process conducted by DAVID (Database for Annotation, Visualization, and Integrated Discovery) using target genes from differential expressed up-regulated miRNAs were negative regulation of translation, positive regulation of transcription, and gene silencing by miRNA. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis from upregulated miRNAs also revealed PI3K-Akt, MAPK, ErbB, aldosterone synthesis and secretion, TGF-β, aldosterone regulated sodium reabsorption, and calcium signaling pathways.
Conclusion
The expression of miRNA from uEVs in patients with GS could provide a physiological role in response to defect of NCC. Further validation and functional study will be performed.
Funding
- Government Support – Non-U.S.