Roth M, Emmons L R, Perruchoud A, Block L H
Department of Research, Kantonsspital, University of Basel, Switzerland.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1888-92. doi: 10.1073/pnas.88.5.1888.
The plausible role that platelet-derived growth factor (PDGF) has in the localized pathophysiological changes that occur in the arterial wall during development of atherosclerotic lesions led us to investigate the influence of recombinant (r)PDGF isomers -AA, -AB, and -BB on the expression of low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase [(S)-mevalonate:NAD+ oxidoreductase (CoA-acylating), EC 1.1.1.88] genes. In addition, we clarified the role of protein kinase C (PKC) in expression of the two genes in human skin fibroblasts and vascular smooth muscle cells. The various rPDGF isoforms are distinct in their ability to activate transcription of both genes: (i) Both rPDGF-AA and -BB stimulate transcription of the LDL-R gene; in contrast, rPDGF-BB, but not -AA, activates transcription of the HMG-CoA reductase gene. (ii) All recombinant isoforms of PDGF activate transcription of the c-fos gene. (iii) While rPDGF-dependent transcription of the LDL-R gene occurs independently of PKC, transcription of the HMG-CoA reductase gene appears to involve the action of that enzyme.
血小板衍生生长因子（PDGF）在动脉粥样硬化病变发展过程中动脉壁局部发生的病理生理变化中可能发挥的作用，促使我们研究重组（r）PDGF异构体-AA、-AB和-BB对低密度脂蛋白受体（LDL-R）和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶[（S）-甲羟戊酸：NAD+氧化还原酶（辅酶A酰化），EC 1.1.1.88]基因表达的影响。此外，我们阐明了蛋白激酶C（PKC）在人皮肤成纤维细胞和血管平滑肌细胞中这两个基因表达中的作用。各种rPDGF异构体在激活这两个基因转录的能力上有所不同：（i）rPDGF-AA和-BB均刺激LDL-R基因的转录；相反，rPDGF-BB而非-AA激活HMG-CoA还原酶基因的转录。（ii）PDGF的所有重组异构体均激活c-fos基因的转录。（iii）虽然rPDGF依赖的LDL-R基因转录独立于PKC发生，但HMG-CoA还原酶基因的转录似乎涉及该酶的作用。
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