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EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway

Ying Chen1, Xinwang Zhu1, Da Sun1

  • 1Department of Nephrology, The First Hospital of China Medical University, No.155 Nanjing Bei Street, Shenyang, Liaoning, China.

Scientific Reports
|November 25, 2024
PubMed

Insights

Circular RNA hsa_circ_0127071 accelerates kidney aging by activating the EIF4A3/JAK2/STAT5 pathway. Targeting this mechanism offers a new strategy for anti-aging therapies and treating kidney disorders.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Nephrology

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cellular processes, including aging.
  • Understanding circRNA mechanisms in cellular senescence is crucial for identifying novel anti-aging therapeutic targets.

Purpose of the Study:

  • To investigate the role and regulatory mechanism of hsa_circ_0127071 in renal aging.
  • To explore hsa_circ_0127071's potential as a therapeutic target for age-related kidney disorders.

Main Methods:

  • High-throughput sequencing to identify differential circRNA expression in young versus old kidney tissues.
  • Quantitative real-time PCR (qRT-PCR) to validate hsa_circ_0127071 expression.
  • Cellular senescence assays (SA-β-Gal, Masson's trichrome staining).
  • RNA Immunoprecipitation (RIP), RNA Pull-Down Assay, and Western Blot (WB) to elucidate molecular interactions.

Main Results:

  • hsa_circ_0127071 expression was significantly elevated in aged kidney tissues compared to young tissues.
  • Silencing EIF4A3, a component of the JAK2/STAT5 pathway, delayed cellular aging.
  • Erythropoietin (EPO) activated the JAK2/STAT5 pathway, increasing senescence in Human glomerular mesangial cells (HGMCs).
  • Losartan (LOS) treatment reduced JAK2/STAT5 activity and delayed HGMC aging.

Conclusions:

  • hsa_circ_0127071 promotes renal aging via the EIF4A3/JAK2/STAT5 signaling axis.
  • This circRNA represents a novel therapeutic target for managing renal aging and related diseases.
Keywords:
Human glomerular mesangial cellsRegulatory mechanismRenal agingSignaling pathway

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