Up-regulation of cyr61 in vascular smooth muscle cells of spontaneously hypertensive rats.
In the present study, we applied a fluorescent differential display method to mRNAs from aortae of spontaneously hypertensive rats (SHRs), stroke-prone spontaneously hypertensive rats (SPSHRs), and their parental strain, Wistar Kyoto rats (WKYRs), to identify the genes involved in the development of hypertension. Through this screen we came across a gene that is consistently up-regulated in hypertensive rats. Nucleotide sequence determination of the corresponding cDNA revealed that the gene is the rat orthologue of cyr61. Northern blot analysis showed that cyr61 expression increases in SHR and SPSHR before the onset of hypertension and is sustained thereafter at higher levels than in age-matched WKYRs. In situ hybridization analysis demonstrated that cyr61 is expressed strongly in smooth muscle cells (SMCs) in media of SHR and SPSHR but not WKYR aorta. Fluorescent in situ hybridization mapped the cyr61 gene to rat chromosome 1p12-13, which is located in close proximity to a recently defined quantitative trait locus including NHE3 Na(+)/H(+) exchanger. Overexpression of the cyr61 gene in stably transfected rat SMC line A7r5 caused rather inhibitory effects on the proliferation and DNA and protein synthesis. Our results thus demonstrate for the first time that cyr61 can also act as a growth inhibitor in SMC of genetically hypertensive rats. This may reveal a new route for investigation of the pathogenesis of hypertension.
Unoki
Hiroyuki
H
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Furukawa
Kenji
K
Yonekura
Hideto
H
Ueda
Yoshimichi
Y
Katsuda
Shogo
S
Mori
Mitsuko
M
Nakagawara
Kan-Ichi
K
Mabuchi
Hiroshi
H
Yamamoto
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D015152:Blotting, Northern; D002874:Chromosome Mapping; D055515:Cysteine-Rich Protein 61; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics* / Q000378:metabolism; D011921:Rats, Inbred WKY; D016415:Sequence Alignment; D015854:Up-Regulation
C501848:CCN1 protein, human; C491850:CCN1 protein, mouse; C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger