IGF-1 released by corneal epithelial cells induces up-regulation of N-cadherin in corneal fibroblasts.
Interactions between epithelial cells and fibroblasts play important roles in tissue homeostasis. With the use of a coculture system in which human corneal fibroblasts and epithelial cells are cultured on opposite sides of a collagen (vitrigel) membrane, we have examined the effects of epithelial cells on expression of the adherens-junction protein N-cadherin in fibroblasts. Reverse transcription-polymerase chain reaction and immunoblot analyses showed that the presence of epithelial cells increased the expression of N-cadherin in fibroblasts at the mRNA and protein levels. This effect of epithelial cells was mimicked by insulin-like growth factor-1 (IGF-1) but not by epidermal growth factor or fibroblast growth factor. Depletion of IGF-1 in epithelial cells by RNA interference abolished the effect of these cells on N-cadherin expression in fibroblasts. The presence of epithelial cells activated the IGF-1 receptor as well as up-regulated expression of the transcriptional regulator ZEB1 in fibroblasts. RNA interference-mediated depletion of IGF-1 in epithelial cells prevented the effect of these cells on ZEB1 expression in fibroblasts. These results suggest that IGF-1 released from corneal epithelial cells up-regulates the expression of N-cadherin in corneal fibroblasts.
Ko
Ji-Ae
JA
Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan. jiae0831@yamaguchi-u.ac.jp
Yanai
Ryoji
R
Nishida
Teruo
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D007334:Insulin-Like Growth Factor I