Dr SOON WEI WONG1,2, Dr DARLING ROJAS-CANALES1,2, Ms ELISE TUCKER2, KYM MCNICHOLAS1, ANNE-SOPHIE MEHDRON2, Dr Jonathan Gleadle1,2
1Department of Renal Medicine, Flinders Medical Centre, Bedford Park, Australia, 2College of Medicine and Public Health, Flinders University, Bedford Park, Australia
Aim:
To examine changes in miRNA expression during compensatory renal hypertrophy (CRH).
Background:
CRH naturally occurs when one kidney is removed for kidney donation or cancer removal. The remaining kidney grows approximately 30% and this is dominated by an increase in individual cell size. MicroRNAs (miRs) have been described to play important post transcriptional roles in growth control. However, their role in CRH remains unknown.
Method:
C57BL6 mice underwent a left kidney nephrectomy (unx) or sham operation. The remaining kidney was collected 24, 48 and 72 hours post-surgery (n=6 per group). RNA was extracted and underwent small RNA-Sequencing. QuickMIRSeq was used to identify and quantify the miRs and edgeR was used for miR differential expression analysis (adjusted p<0.05 was used to determine significance). MultiMiR was used to retrieve miRNA-target interactions from pre-existing RNA-seq data to perform pathway enrichment analysis. Results: Significant differential expression of miRs were only detected at 48h and 72h timepoints. At 48h, 24 miRs were differentially expressed (19 upregulated and 5 downregulated), of those upregulated, 6 belong to the Let-7 family (Let-7a,b,c,f,g,i). At 72h only 5 miRs were differentially expressed of which 1 was from the Let-7 family (Let-7a). Subsequent enrichment analysis of Let-7 family miR gene targets at 48h suggested a decrease in genes with roles in mitotic spindle assembly and inhibition of mTORC signalling.
Conclusion:
Let-7 miR family members were upregulated at 48 and 72h post nephrectomy. These microRNAs have been previously implicated in cell cycle control and in nephrogenesis. Our enrichment analysis suggests that expression of Let-7 miRs may be involved in cell cycle and contribute to the cellular hypertrophy seen in CRH.
Biography:
I am currently undertaking a post-doctoral position at Flinders Medical Centre. My research focuses on the mechanism underlying healthy compensatory kidney growth. When a healthy individual donates a kidney, their remaining kidney increase in size and excretory function by over 30%. The mechanism responsible for compensatory renal hypertrophy remains elusive. Therefore, my research aims to identify how the early growth signal is generated, how it is targeted to the kidney and what are the metabolic alterations required to generate hypertrophy.