Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative disease.
The hepatocyte growth factor (HGF) has been crucially implicated in the development of proliferative retinal diseases; however, it is unclear whether retinal glial cells express or respond to HGF. Therefore, we examined the expression of HGF and of the receptor for HGF, c-Met, by immunohistochemical costaining with glial fibrillary acidic protein (GFAP) in epiretinal membranes of patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), respectively. Furthermore, it was determined whether cells of the human retinal glial cell line, MIO-M1, secrete HGF protein, and whether HGF stimulates proliferation and chemotaxis, and secretion of the vascular endothelial growth factor (VEGF). Neuroretinas of patients with PVR express elevated mRNA level for HGF in comparison to control retinas. In epiretinal membranes of patients with PVR or PDR, immunoreactivity for HGF and for c-Met, respectively, partially colocalized with immunoreactivity for GFAP. Fetal bovine serum and basic fibroblast growth factor, but not heparin-binding epidermal or platelet-derived growth factors, evoked HGF secretion by cultured retinal glial cells. HGF displayed only a marginal effect on cell proliferation while it stimulated chemotaxis. HGF promoted the secretion of VEGF, via activation of the phosphatidylinositol-3 kinase. It is concluded that glial cells in epiretinal membranes express both HGF protein and c-Met receptors. The results suggest an autocrine/paracrine role of HGF in glial cell responses during proliferative vitreoretinal disorders as well as in retinal neovascularization, by stimulating of VEGF release.
Hollborn
Margrit
M
Department of Ophthalmology, University Eye Clinic, Leipzig, Germany.
Krausse
Christian
C
Iandiev
Ianors
I
Yafai
Yousef
Y
Tenckhoff
Solveig
S
Bigl
Marina
M
Schnurrbusch
Ute E K
UE
Limb
G Astrid
GA
Reichenbach
Andreas
A
Kohen
Leon
L
Wolf
Sebastian
S
Wiedemann
Peter
P
Bringmann
Andreas
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D017931:DNA Primers; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met