HB-EGF is produced in the peritoneal cavity and enhances mesothelial cell adhesion and migration.
BACKGROUND
The mesothelial cell monolayer lining the peritoneal membrane needs constant repair in response to peritonitis and to the toxicity of peritoneal dialysate. In many continuous ambulatory peritoneal dialysis (CAPD) patients, the repair process progressively fails, and membrane dysfunction and fibrosis occur. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has an important role in wound repair and is also fibrogenic, and thus may be involved in these processes in the peritoneal cavity.


METHODS
The presence of HB-EGF, its receptors, and its associated proteins was determined in peritoneal membrane biopsies, cultured human peritoneal mesothelial cells (HPMCs), and peritoneal macrophages from CAPD patients by reverse transcription-polymerase chain reaction, flow cytometry, and immunofluorescence immunocytochemistry with confocal microscopy. HB-EGF effects on HPMC adhesion were measured by a static adhesion assay, on integrin expression by flow cytometry, and on migration by wound healing and chemotaxis assays.


RESULTS
HB-EGF, its receptors HER-1 and HER-4, and the associated proteins CD9, CD44, and integrin alpha(3)beta(1) were expressed by HPMCs and peritoneal macrophages. HB-EGF colocalized with HER-1 and HER-4 in HPMCs and induced their adhesion to collagen type I, expression of beta 1 integrins, and migration.


CONCLUSIONS
HB-EGF is produced by cells in the peritoneal cavity of CAPD patients and has functional effects on HPMCs that would facilitate repair of the mesothelial layer.
Faull
R J
RJ
Renal Laboratory, Royal Adelaide Hospital, Adelaide, South Australia. rfaull@mail.rah.sa.gov.au
Stanley
J M
JM
Fraser
S
S
Power
D A
DA
Leavesley
D I
DI
D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010529:Peritoneal Cavity / Q000502:physiology*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014018:Tissue Distribution
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors