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Updated: Jul 11, 2025

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

Published on: November 10, 2021

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Epidermal growth factor receptor activation is essential for kidney fibrosis development

Shirong Cao1,2, Yu Pan1,2,3, Andrew S Terker1,2

  • 1Division of Nephrology and Hypertension, Department of Medicine, Nashville, TN, USA.

Nature Communications
|November 14, 2023
PubMed

Insights

Epidermal Growth Factor Receptor (EGFR) is crucial for kidney fibrosis development, driving fibroblast migration and proliferation before other factors induce myofibroblast transformation. Selective EGFR deletion in specific cells inhibits kidney fibrosis progression.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Medicine

Background:

  • Fibrosis, characterized by excess extracellular matrix accumulation, can lead to organ failure and lacks specific treatments.
  • The Epidermal Growth Factor Receptor (EGFR) signaling pathway is linked to kidney fibrosis, but its direct role remains unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which EGFR mediates kidney fibrosis.
  • To investigate the role of EGFR in fibroblast/pericyte activation and subsequent myofibroblast transformation.

Main Methods:

  • Analysis of EGFR expression in human and mouse fibrotic kidneys.
  • Selective EGFR deletion in fibroblast/pericyte populations in vivo.
  • In vivo and in vitro functional studies.
  • Single-nucleus RNA sequencing.

Main Results:

  • EGFR expression is upregulated in interstitial myofibroblasts in fibrotic kidneys.
  • Selective EGFR deletion in fibroblasts/pericytes significantly inhibited kidney fibrosis induced by various insults.
  • EGFR activation promotes initial pericyte/fibroblast migration and proliferation, preceding TGF-ß-mediated myofibroblast transformation.

Conclusions:

  • EGFR plays a critical, early role in driving kidney fibrosis by promoting fibroblast/pericyte migration and proliferation.
  • Targeting EGFR may offer a novel therapeutic strategy for kidney fibrosis and potentially fibrosis in other organs.

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