Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-9-18
pubmed:abstractText
Members of the epidermal growth factor (EGF) family and their receptors are involved in many cellular processes, including proliferation, migration, and differentiation. We have previously reported that these growth factors are expressed and have specific regulatory functions in an organ-like culture model of normal human urothelial cells. Here, we used this model to investigate the involvement of EGF receptor (EGFR) in human urothelial regeneration. Three 4-mm-diameter damaged areas were made in confluent normal human urothelial cell cultures with a biopsy punch. Regeneration was measured, on fixed stained cultures, with an image analyzer, at 4, 24, and 48 hours after injury. Cell proliferation was assessed by 5-bromo-2-deoxyuridine incorporation. To identify EGF family factors potentially involved in the healing process, we studied the effect of these factors on damaged confluent cultures and the level of expression of mRNAs extracted from these cultures. EGFR inhibition of the proliferation and migration of urothelial cells was tested with (1). a specific tyrosine kinase inhibitor (AG1478) and (2). a blocking anti-EGFR antibody (LA22). Exogenously added amphiregulin, EGF, transforming growth factor-alpha and heparin-binding EGF (HB-EGF) stimulated urothelial regeneration. The damaged areas were repaired by regrowth within 48 hours. Both AG1478 and LA22 inhibited the repair (by 50% and 30%, respectively), as well as proliferation and migration. This regeneration was accompanied by increased HB-EGF mRNA expression in cultures of cells from four of six subjects, but no corresponding change in EGFR protein level was observed. These results indicate that the EGFR signaling pathway is involved in urothelial regeneration. Our data support an autocrine role of HB-EGF in this process and suggest that the EGFR pathway is a potential therapeutic target for modulating urothelial cell proliferation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Blocking, http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine, http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers, http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins, http://linkedlifedata.com/resource/pubmed/chemical/amphiregulin, http://linkedlifedata.com/resource/pubmed/chemical/heparin-binding EGF-like growth..., http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG 1478
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1333-41
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:13679441-Antibodies, Blocking, pubmed-meshheading:13679441-Blotting, Western, pubmed-meshheading:13679441-Bromodeoxyuridine, pubmed-meshheading:13679441-Cell Division, pubmed-meshheading:13679441-Cell Movement, pubmed-meshheading:13679441-Cells, Cultured, pubmed-meshheading:13679441-DNA Primers, pubmed-meshheading:13679441-Epidermal Growth Factor, pubmed-meshheading:13679441-Glycoproteins, pubmed-meshheading:13679441-Humans, pubmed-meshheading:13679441-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:13679441-RNA, Messenger, pubmed-meshheading:13679441-Receptor, Epidermal Growth Factor, pubmed-meshheading:13679441-Regeneration, pubmed-meshheading:13679441-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:13679441-Time Factors, pubmed-meshheading:13679441-Transforming Growth Factor alpha, pubmed-meshheading:13679441-Tyrphostins, pubmed-meshheading:13679441-Urothelium, pubmed-meshheading:13679441-Wound Healing
pubmed:year
2003
pubmed:articleTitle
Epidermal growth factor receptor regulates normal urothelial regeneration.
pubmed:affiliation
INSERM EMI 03.37, Centre de Recherches Chirurgicales, Faculté de Médecine, Université de Paris 12, Créteil, France.
pubmed:publicationType
Journal Article