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Updated: Jul 3, 2026

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
10:15

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

Activating transcription factor 3 aggravates renal fibrosis by regulating EGR2-mediated autophagy

Ruiwei Yan1, Anni Song1, Mingcun Hu1

  • 1Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Translational Research : the Journal of Laboratory and Clinical Medicine
|July 1, 2026
PubMed
Abstract

Insights

Activating transcription factor 3 (ATF3) exacerbates chronic kidney disease (CKD) fibrosis by promoting extracellular matrix deposition and renal tubular atrophy. Targeting ATF3 may offer a novel therapeutic strategy for kidney fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Chronic kidney disease (CKD) affects 10% of the global population, characterized by renal fibrosis.
  • Autophagy's role in renal fibrosis is significant, but regulatory mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of activating transcription factor 3 (ATF3) in renal fibrosis.
  • To elucidate the underlying mechanisms of ATF3 in kidney fibrosis.

Main Methods:

  • Utilized unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI) mouse models.
  • Employed immunohistochemistry, western blot, and RT-qPCR to confirm ATF3 expression.
  • Generated ATF3 knockdown mice using adeno-associated virus (AAV) and conducted in vitro experiments with BUMPT cell lines.

Main Results:

  • ATF3 expression was significantly elevated in kidney tissues from UUO and UIRI mouse models.
  • ATF3 knockdown attenuated extracellular matrix (ECM) deposition and epithelial-mesenchymal transition (EMT).
  • Transcriptomic analysis revealed ATF3's involvement in autophagy and identified early growth response protein 2 (EGR2) as a downstream target.

Conclusions:

  • Enhanced ATF3 expression contributes to renal fibrosis.
  • ATF3 regulates EGR2-mediated autophagy pathways, promoting kidney fibrosis.
  • Targeting ATF3 presents a potential therapeutic avenue for renal fibrosis.
Keywords:
Activating transcription factor 3AutophagyEarly growth response protein 2Renal fibrosisTranscriptomic analyses

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