Anna Means
Assistant Professor
Last active: 3/27/2020

Epidermal growth factor receptor regulates pancreatic fibrosis.

Blaine SA, Ray KC, Branch KM, Robinson PS, Whitehead RH, Means AL
Am J Physiol Gastrointest Liver Physiol. 2009 297 (3): G434-41

PMID: 19608732 · PMCID: PMC2739824 · DOI:10.1152/ajpgi.00152.2009

The development of pancreatic fibrosis has been shown to be a major component in several diseases of the pancreas including pancreatic cancer, chronic pancreatitis, and type 2 diabetes mellitus, but its actual role in the progression of these disorders is still unknown. This fibrosis is characterized by stromal expansion and the excessive deposition of extracellular matrix (ECM) that replaces pancreatic tissue. This eventually leads to dysregulation of ECM turnover, production of cytokines, restriction of blood flow, and often exocrine and endocrine insufficiencies. Activated pancreatic stellate cells (PSCs) have been identified as key mediators in the progression of pancreatic fibrosis, serving as the predominant source of excess ECM proteins. Previously, we found that overexpression of the growth factor heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pancreatic islets led to intraislet fibrosis. HB-EGF binds to and activates two receptors, epidermal growth factor receptor (EGFR) and ErbB4, as well as heparin moieties and CD9/DRAP27. To understand the mechanism underlying the induction of fibrogenesis by HB-EGF, we utilized a hypomorphic allele of Egfr, the Waved-2 allele, to demonstrate that EGFR signaling regulates fibrogenesis in vivo. Using an in vitro cell migration assay, we show that HB-EGF regulates both chemoattraction and stimulation of proliferation of PSCs via EGFR activation.

MeSH Terms (19)

Animals Cell Line Cell Proliferation Chemotaxis Disease Models, Animal ErbB Receptors Fibrosis Heparin-binding EGF-like Growth Factor Homeodomain Proteins Intercellular Signaling Peptides and Proteins Mice Mice, Inbred C57BL Mice, Transgenic Mutation Pancreas Pancreatic Diseases Recombinant Proteins Signal Transduction Trans-Activators

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