N 6-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy

Hua Shi1,2,3, Tianchao Xiang1,2,3, Jiayan Feng4

  • 1Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.

Insights

RNA epigenetic modification N6-methyladenosine (m6A) methylation is implicated in congenital anomalies of the kidneys and urinary tracts (CAKUT). This study reveals differential m6A patterns in obstructive megaureter versus reflux uropathy.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Developmental Biology

Background:

  • Congenital anomalies of the kidneys and urinary tracts (CAKUT) are the leading cause of pediatric renal failure.
  • RNA epigenetic modification N6-methyladenosine (m6A) methylation is crucial for organ development.
  • The role of m6A methylation in CAKUT pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the m6A methylomic landscape in CAKUT.
  • To explore the role of m6A methylation in the pathogenesis of obstructive megaureter and primary vesicoureteral reflux.

Main Methods:

  • Utilized m6A-mRNA epitranscriptomic microarray to analyze ureter tissue from children with obstructive megaureter (M group) and primary vesicoureteral reflux (V group).
  • Employed real-time PCR to assess mRNA levels of m6A readers/writers and erasers.
  • Integrated m6A methylome and transcriptome data to identify differentially methylated and expressed mRNAs.

Main Results:

  • Identified 228 differentially methylated mRNAs between the M and V groups, impacting various signaling pathways.
  • Observed significantly higher mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2, WTAP) and lower levels of the eraser FTO in the M group.
  • Discovered 298 hypermethylated and 489 hypomethylated mRNAs with differential expression in the M group compared to the V group.

Conclusions:

  • The findings highlight the involvement of m6A methylation in the pathogenesis of obstructive and reflux uropathy.
  • m6A methylation patterns differ significantly between obstructive megaureter and primary vesicoureteral reflux.
  • This study provides novel insights into the epigenetic mechanisms underlying CAKUT.
Abstract

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