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Abstract: PO1220

Analysis of MicroRNAs as Regulators of Expression of Transcripts Associated with Stem Cell Pluripotency in Pkd1-Deficient Mouse Models

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Moyano muñoz, Juan José augusto, Universidade Federal de São Paulo, São Paulo, Brazil, São Paulo, SP, Brazil
  • Boim, Mirian A., Universidade Federal de São Paulo, São Paulo, Brazil, São Paulo, SP, Brazil
  • Onuchic, Luiz F., University of São Paulo School of Medicine, São Paulo, SP, Brazil
  • Heilberg, Ita Pfeferman, Universidade Federal de São Paulo, São Paulo, Brazil, São Paulo, SP, Brazil
Background

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cysts formation deriving from collecting ducts. Pluripotent stem cells associated with the formation of renal structures have been used in in vitro studies of nephrogenesis or cystogenesis related to ADPKD. However, the association between transcripts integrating pathways involved in stem cells pluripotency and cystogenesis deserves further investigation.The microRNAs (miRNAs) that participate in the regulation of these transcripts in kidney tissues of mouse models orthologous to ADPKD have not yet been validated.To identify regulatory miRNAs and differently expressed transcripts associated with stem cell pluripotency in kidney tissues of Pkd1-deficient mouse models.

Methods

A transcriptomic computational identification and validation of the expression level of regulatory miRNAs and genes by RT-qPCR, normalized by their respective housekeepings, miR-26a and Ppia was performed. The analyses were performed on kidneys from 10- to 12-week-old cystic mice (Pkd1flox/flox:Nestincre or Pkd1flox/-:Nestincre, CY, n = 10) and their non-cystic controls (Pkd1flox/flox or Pkd1flox/-, NC, n = 10); mice haploinsufficient for Pkd1 (Pkd1+/-, HT, n = 6) and their wild controls (Pkd1+/+, WT, n = 6); and 15-day-old severely cystic mice (Pkd1V/V, SC, n = 7) and their controls (CO, n = 5).

Results

The validation of the computational analyses performed in our three animal models with reports from the literature in other Pkd1-deficient models, identified 10 differently expressed genes associated with the regulation of stem cells pluripotency. Increased expression of Stat3 and Map3k1 genes and decreased regulatory miRNA Let-7a were observed in SC versus CO kidneys. On the other hand, Mapk14 gene showed decreased expression while its potential regulator, miR-21, revealed increased expression in SC versus CO kidneys. Fgf10 expression was decreased in SC versus CO kidneys whereas a trend of increased expression in the CY versus NC group has been observed.

Conclusion

Present results suggest a potential regulatory effect of miR-21 on Mapk14 expression and of miR-Let-7a on the expression of Stat3, Map3k1 and Fgf10, namely transcripts involved in stem cells pluripotency and cystogenesis in kidney tissues of Pkd1-deficient mouse models.

Funding

  • Government Support – Non-U.S.