Epidermal growth factor receptor paracrine upregulation in idiopathic pulmonary fibrosis fibroblasts is blocked by nintedanib

American Journal of Physiology. Lung Cellular and Molecular Physiology
Gali Epstein ShochetDavid Shitrit

Abstract

Although present in normal cells, epidermal growth factor receptor (EGFR) is overexpressed in a variety of tumors and has been associated with decreased survival. Because activated fibroblasts are considered key effectors in fibrosis and because metastatic and fibrotic processes were shown to share similar signaling pathways, we investigated the contribution of EGFR signaling to idiopathic pulmonary fibrosis (IPF) progression in lung fibroblasts derived from patients with IPF (IPF-HLF). EGFR expression and EGFR-related signaling were evaluated by Western blot and immunohistochemistry. Supernatants (SN) from cultured IPF-HLF and N-HLF were added to N-HLF, and their effect on cell phenotype was tested. Growth factor levels in the SN were measured by ELISA-based arrays. EGFR activity was blocked by erlotinib (Tarceva, 0.1-0.5 µM). Expression of EGFR, phosphorylated (p)EGFR-1068 and pAkt-473 was significantly higher in IPF-HLF compared with lung fibroblasts from control donors (N-HLF) (P < 0.05). Apparent expression of p/total EGFR and pAkt-473 was found in the myofibroblastic foci of IPF patients. Erlotinib significantly inhibited IPF-HLF but not N-HLF proliferation. IPF-HLF-SN elevated N-HLF cell number, viability, EGFR expressio...Continue Reading

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Citations

Sep 29, 2019·Journal of Clinical Medicine·JanWillem DuitmanC Arnold Spek
Jan 23, 2020·International Journal of Molecular Sciences·Dongsheng Jiang, Yuval Rinkevich
Jul 9, 2020·Therapeutic Advances in Chronic Disease·Gali Epstein ShochetDavid Shitrit
Nov 11, 2020·Therapeutic Advances in Respiratory Disease·Yunguan WangAnil G Jegga
May 1, 2021·Cells·Shuying Yang, Sergey V Plotnikov

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Methods Mentioned

BETA
biopsy
PCR
antibody array

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GraphPad
GraphPad Prism

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