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Heparin Binding‐Epidermal Growth Factor and Src Family Kinases in Proliferation of Renal Epithelial Cells
Author(s) -
Zhuang Shougang,
Kinsey Gilbert R.,
Rasbach Kyle
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.728.11
Subject(s) - heparin binding egf like growth factor , microbiology and biotechnology , autocrine signalling , paracrine signalling , epidermal growth factor , proto oncogene tyrosine protein kinase src , receptor , chemistry , kinase , biology , biochemistry
This study was to identify the endogenous EGF receptor ligand and investigate the mechanism(s) by which RPTC proliferate. RPTC expressed both pro‐ and cleaved heparin binding epidermal growth factor (HB‐EGF) forms and several metalloproteinases (MMP‐2, ‐3 ‐9, and ADAM10, ADAM17) that have been reported to cleave HB‐EGF. Treatment of RPTC with CRM 197, an inhibitor of HB‐EGF binding to EGF receptor, or down‐regulation of HB‐EGF with siRNA inhibited RPTC proliferation following plating. Furthermore, blocking metalloproteinases with GM6001, TAPI‐1, GW280264X, but not GI254023X, attenuated the proliferation following plating. Although EGF receptor activation is required for RPTC proliferation following oxidant injury, CRM197, GM6001, and TAPI‐1 did not block this response. In contrast, inhibition of Src with PP1 blocked EGF receptor activation and RPTC proliferation in oxidant‐injured RPTC. In addition, PP1 treatment attenuated HB‐EGF‐enhanced RPTC proliferation. We suggest that RPTC proliferation following plating is regulated by HB‐EGF produced through an autocrine/paracrine mechanism and RPTC proliferation following oxidant injury is mediated by Src without involvement of HB‐EGF production.