Outcomes of transcatheter aortic valve replacement (TAVR) in patients receiving chronic dialysis in Australia and New Zealand using data-linkage
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Palamuthusingam, Dharmenaan
Hawley, Carmel
Pascoe, Elaine
Johnson, David
Hayman, Sam
Sivalingam, Palvannan
Mcdonald, Stephen
Boudville, Neil
Jose, Matthew
Puri, Pria
Talaulikar, Girish
Cross, Nick
Fahim, Magid
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Sydney, Australia
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Abstract
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 h 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 48 h and 72 h timepoints. At 48 h, 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 72 h 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 48 h 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 72 h 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.
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Nephrology
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27
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S1
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Clinical sciences
Nephrology and urology
Cardiovascular medicine and haematology
Life Sciences & Biomedicine
Science & Technology
Urology & Nephrology
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Scalia, I; Palamuthusingam, D; Hawley, C; Pascoe, E; Johnson, D; Hayman, S; Sivalingam, P; Mcdonald, S; Boudville, N; Jose, M; Puri, P; Talaulikar, G; Cross, N; Fahim, M, Outcomes of transcatheter aortic valve replacement (TAVR) in patients receiving chronic dialysis in Australia and New Zealand using data-linkage, Nephrology, 2022, 27 (S1), pp. 75-75