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Abstract: SA-PO542

Hypoxia-Regulated MicroRNA-210 Expression and Role in Nephrogenesis

Session Information

  • Developmental Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology

Authors

  • Hemker, Shelby L., Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
  • Clugston, Andrew Scott, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
  • Phua, Yu Leng, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
  • Ho, Jacqueline, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
  • Kostka, Dennis, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Background

Placental insufficiency causes fetal hypoxia, reduced blood flow to the kidneys, and is the main cause of intrauterine growth restriction (IUGR). IUGR and fetal hypoxia adversely affects kidney development, resulting in decreased nephron number and increased chance of congenital anomalies of the kidney and urinary tract (CAKUT), the leading cause of kidney failure in children. Furthermore, IUGR puts affected individuals at an increased risk for developing hypertension and chronic kidney disease. We hypothesize that key regulators of normal kidney development are responsive to changes in oxygen tension. microRNA-210 (miR-210) is the most consistently induced miRNA in hypoxia and is directly regulated by the Hypoxia Inducible Factor (HIF) transcription factor family. microRNAs (miRNAs) are ~22nt small noncoding RNAs that fine-tune gene expression through post-transcriptional regulation of specific target mRNAs and are essential for proper mammalian development.

Methods

First, we defined miR-210 expression throughout murine kidney development using small RNA sequencing and in situ hybridization. Then, we cultured ex vivo kidney explants in different oxygen levels and examined the effect on both miRNA and mRNA expression through RNA sequencing. Furthermore, we investigated the effect of a global miR-210 mouse knockout on kidney development using real time RT-qPCR and histological analyses.

Results

We found that miR-210 is broadly expressed in the developing kidney, including in nephron progenitors (cells that differentiate to form the nephron) and ureteric bud epithelium (cells that form the collecting duct system). Our transcriptomic studies found that miR-210 is upregulated in hypoxia, while several of its target mRNAs are down-regulated. Most interstingly, the miR-210 knockout mouse has altered expression of key genes in nephron progenitors, ureteric bud, and endothelial cells during kidney development.

Conclusion

Together, our data suggests that miR-210 plays a role in normal kidney development.

Funding

  • NIDDK Support