Saltis J, Bobik A
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
J Hypertens. 1995 Dec;13(12 Pt 1):1441-8.
To investigate the developmental regulation of transforming growth factor-beta 1 (TGF-beta 1) action and the expression of TGF-beta receptors in vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR).
TGF-beta 1 effects on proliferation and expression of TGF-beta receptor subtypes were compared in VSMC prepared from SHR, Wistar-Kyoto (WKY) and Sprague-Dawley rats of different ages.
TGF-beta 1 effects on platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferation were examined in VSMC isolated from SHR, WKY and Sprague-Dawley rats aged 1, 4 and 12 weeks, and from renal hypertensive WKY rats. TGF-beta receptors on the surface of VSMC were identified by affinity labelling, followed by immunoprecipitation with TGF-beta receptor antibodies; complexes were then analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
TGF-beta 1 inhibited by 60-80% PDGF-BB-stimulated proliferation of VSMC from 1-week-old SHR. In 4-week-old SHR, VSMC were resistant to the antiproliferative action of TGF-beta 1, whereas the mitogenic activity of PDGF-BB was increased approximately 150% by TGF-beta 1 in VSMC from 12-week-old SHR. In contrast, TGF-beta 1 inhibited by 10-50% PDGF-BB-stimulated proliferation of VSMC from age-matched WKY and Sprague-Dawley rats. TGF-beta isoforms (TGF-beta 1, -beta 2, -beta 3) all elicited similar growth responses in VSMC from SHR and WKY rats of different ages. Hypertension per se did not alter TGF-beta 1 effects on proliferation, as TGF-beta 1 inhibited by 30-40% growth factor action on VSMC from control, uni-nephrectomized and one-kidney one-clip hypertensive WKY rats. The type I, II and III TGF-beta receptors were expressed on the surface of VSMC isolated from SHR of different ages.
Alterations in TGF-beta 1 responses, which become evident in VSMC from 4-week-old SHR and are most prominent at 12 weeks, may be important in the development of vascular hypertrophy in this rat strain.
研究自发性高血压大鼠（SHR）血管平滑肌细胞（VSMC）中转化生长因子-β1（TGF-β1）作用的发育调控及TGF-β受体的表达。
比较不同年龄的SHR、Wistar-Kyoto（WKY）和Sprague-Dawley大鼠制备的VSMC中TGF-β1对增殖及TGF-β受体亚型表达的影响。
检测1周龄、4周龄和12周龄的SHR、WKY和Sprague-Dawley大鼠以及肾性高血压WKY大鼠分离的VSMC中TGF-β1对血小板衍生生长因子-BB（PDGF-BB）刺激增殖的影响。通过亲和标记鉴定VSMC表面的TGF-β受体，然后用TGF-β受体抗体进行免疫沉淀；接着通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析复合物。
TGF-β1抑制1周龄SHR的VSMC中60%-80%的PDGF-BB刺激的增殖。在4周龄的SHR中，VSMC对TGF-β1的抗增殖作用有抗性，而在12周龄的SHR的VSMC中，TGF-β1使PDGF-BB的促有丝分裂活性增加约150%。相比之下，TGF-β1抑制年龄匹配的WKY和Sprague-Dawley大鼠的VSMC中10%-50%的PDGF-BB刺激的增殖。TGF-β亚型（TGF-β1、-β2、-β3）在不同年龄的SHR和WKY大鼠的VSMC中均引发相似的生长反应。高血压本身并未改变TGF-β1对增殖的影响，因为TGF-β1抑制对照、单侧肾切除和单肾单夹高血压WKY大鼠的VSMC中30%-40%的生长因子作用。I型、II型和III型TGF-β受体在不同年龄SHR分离的VSMC表面表达。
TGF-β1反应的改变在4周龄SHR的VSMC中明显，在12周时最为突出，这可能在该大鼠品系血管肥大的发展中起重要作用。
