2. Academic Validation
  3. Myeloid EGFR deficiency accelerates recovery from AKI via macrophage efferocytosis and neutrophil apoptosis

Myeloid EGFR deficiency accelerates recovery from AKI via macrophage efferocytosis and neutrophil apoptosis

  • Nat Commun. 2025 May 16;16(1):4563. doi: 10.1038/s41467-025-59393-y.
Yu Pan # 1 2 3,  Shirong Cao # 1 2,  Yinqiu Wang # 1 2,  Jiaqi Tang 1 2,  Aolei Niu 1 2,  Sarah Abu Kar 1 2,  Mengdi Jiang 1 2,  Fenfen Peng 1 2,  Gabriela M Siew 1 2,  Wentian Lu 1 2,  Suwan Wang 1 2,  Matthew Wilson 1 2 4,  Craig Brooks 1 2,  Agnes B Fogo 5,  Andrew S Terker 1 2,  Juan Pablo Arroyo Ornelas 1 2,  Jianchun Chen 1 2,  Ming-Zhi Zhang 6 7,  Raymond C Harris 8 9 10
Affiliations

Affiliations

  • 1 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 2 Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 3 Division of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Veterans Affairs Hospital, Nashville, TN, USA.
  • 5 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 6 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. ming-zhi.zhang@vumc.org.
  • 7 Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA. ming-zhi.zhang@vumc.org.
  • 8 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. ray.harris@vumc.org.
  • 9 Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA. ray.harris@vumc.org.
  • 10 Department of Veterans Affairs Hospital, Nashville, TN, USA. ray.harris@vumc.org.
  • # Contributed equally.
PMID: 40379634 DOI: 10.1038/s41467-025-59393-y
Abstract

Altered expression and activation of Epidermal Growth Factor Receptor (EGFR) is implicated in acute and chronic kidney injury. One of the important cellular sources of EGFR is the myeloid compartment, which plays roles in both acute kidney injury and subsequent fibrosis. Here we show in a murine ischemic acute kidney injury (AKI) model that myeloid deletion of EGFR promotes a pro-resolving, anti-inflammatory phenotype and increased efferocytotic capacity in macrophages. This leads to accelerated recovery in response to AKI and inhibited subsequent development of tubulointerstitial fibrosis. We find that selective EGFR deletion in neutrophils also accelerates recovery from ischemic kidney injury and reduces subsequent fibrosis. EGFR activation plays an essential role in increasing the life span of neutrophils in the injured kidney. Deletion of EGFR expression either in all murine myeloid cells or selectively in neutrophils decreases kidney neutrophil Mcl-1 expression and promotes neutrophil Apoptosis, which is accompanied by accelerated recovery from organ injury and reduced subsequent fibrosis. These studies thus identify coordinated and complementary roles for EGFR activation in neutrophils and macrophages to exacerbate kidney injury.

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