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LncR-GAS5 decrease in adenine phosphoribosyltransferase expresssion via binding TAF1 to increase kidney damage

Wei Liu1,2, Wukaiyang Liang1,2, CunTai Zhang1,2

  • 1Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.

Heliyon
|July 12, 2024
PubMed
Abstract

Insights

Long noncoding RNA GAS5 binds TAF1 to suppress APRT, worsening chronic intermittent hypoxia-induced kidney injury in rats. Reducing GAS5 or increasing APRT alleviates renal damage, apoptosis, and fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genetics

Background:

  • Obstructive sleep apnea-hypopnea syndrome (OSAHS) causes chronic kidney disease (CKD) via chronic intermittent hypoxia (CIH)-induced renal injury.
  • The interaction between long noncoding RNA (lncRNA) GAS5 and adenine phosphoribosyltransferase (APRT) in CIH-induced renal injury is not well understood.

Purpose of the Study:

  • To investigate the interaction between lncRNA GAS5 and APRT in the context of CIH-induced renal injury.
  • To elucidate the molecular mechanisms underlying CIH-induced kidney damage involving GAS5 and APRT.

Main Methods:

  • Established a rat model of chronic intermittent hypoxia (CIH).
  • Utilized transcriptome sequencing, plasmid transfection (sh-GAS5, OE-APRT), RT-qPCR, western blotting, and TUNEL staining.
  • Performed RNA pull-down, RIP, and ChIP assays to verify molecular interactions.

Main Results:

  • CIH significantly increased TAF1 and decreased APRT expression in rat kidneys.
  • GAS5 suppression or APRT overexpression attenuated CIH-induced renal injury, reducing BUN and creatinine levels.
  • GAS5 and TAF1 were found to negatively regulate APRT transcription, with GAS5 binding to TAF1.

Conclusions:

  • lncRNA GAS5 interacts with TAF1 to suppress APRT transcription.
  • This interaction exacerbates chronic intermittent hypoxia-induced renal injury in rats.
  • Targeting the GAS5-TAF1-APRT axis may offer therapeutic potential for CIH-related kidney disease.
Keywords:
APRTCIHRenal injuryTAF1lncRNA GAS5

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