Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in vascular smooth muscle cells.
Keratinocyte growth factor receptor (KGFR), also known as fibroblast growth factor receptor (FGFR)2 IIIb, is located in many types of epithelial cells and is activated by four known ligands (FGF-1, FGF-3, FGF-7 (also known as KGF) and FGF-10) that are predominantly synthesized by mesenchymal cells. In the early stage of atherosclerosis, vascular smooth muscle cells (VSMC) transform from a contractile to a synthetic phenotype, proliferate and migrate into the intima. Previously, FGF-7 mRNA expression was reported in VSMC, but KGFR mRNA was not detected. In the present study, we attempted to determine whether KGFR is localized in VSMC cultured from rat aorta and VSMC in human normal and atherosclerotic coronary arteries. Expression of KGFR mRNA and its protein was detected in cultured rat VSMC by reverse transcription-polymerase chain reaction and western blot analysis, respectively. Immunohistochemically, KGFR was localized in the VSMC of the outer layer of the media in normal human coronary arteries. Furthermore, it was localized in the VSMC of the media and thickened intima of atherosclerotic arteries. Recombinant FGF-7 and/or FGF-10 proteins stimulated the growth of cultured rat VSMC. These findings indicate that KGFR localized in VSMC may contribute to the proliferation of VSMC in normal and atherosclerotic arteries.
Onda
Munehiko
M
Department of Pathology, Nippon Medical School and Division of Surgical Pathology, Nippon Medical School Hospital, Tokyo, Japan. baltan-5@nms.ac.jp
Naito
Zenya
Z
Wang
Ruojiao
R
Fujii
Takenori
T
Kawahara
Kiyoko
K
Ishiwata
Toshiyuki
T
Sugisaki
Yuichi
Y
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D004338:Drug Combinations; D051526:Fibroblast Growth Factor 10; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; C496365:FGFR3 protein, human; C496356:Fgfr2 protein, rat; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3