Wolf G, Haberstroh U, Neilson E G
Renal-Electrolyte Section, University of Pennsylvania, Philadelphia 19104-6144.
Am J Pathol. 1992 Jan;140(1):95-107.
A murine mesangial cell line (MMC) was established from the glomeruli of SJL mice to study the influence of angiotensin II (ANG II) on their growth and function in a serum-free culture. Murine mesangial cells exhibit the phenotypic characteristics of mesangial cells, including staining for desmin, vimentin, Thy 1, and types I and IV collagen by immunofluorescence. The addition of daily doses of 10(-6) to 10(-11) mol/l ANG II to MMCs also induced their proliferation in serum-free media. This effect on growth was independent of the presence of insulin in the media, and was receptor mediated, because the specific ANG II-receptor antagonist DuP 753 abolished proliferative growth. Angiotensin II also stimulated mainly the biosynthesis of type I collagen in our MMCs. Transfection of MMCs with chimeric genes containing enhancer/promoter elements for alpha 2(I) and alpha 1(IV) collagens linked to a chloramphenicol acetyltransferase reporter demonstrated that the stimulatory effect of ANG II for type I depends, at least to some extent, on an increase in transcription. These findings indicate collectively that ANG II in serum-free cultures can be a paracrine catalyst for the growth and biosynthesis of type I collagen in mesangial cells.
为了研究血管紧张素II(ANG II)在无血清培养条件下对小鼠系膜细胞生长和功能的影响,我们从SJL小鼠的肾小球中建立了一种小鼠系膜细胞系(MMC)。小鼠系膜细胞表现出系膜细胞的表型特征,包括通过免疫荧光法检测结蛋白、波形蛋白、Thy 1以及I型和IV型胶原的染色。向MMC中每日添加10^(-6)至10^(-11) mol/l的ANG II也能在无血清培养基中诱导其增殖。这种对生长的影响与培养基中胰岛素的存在无关,且是受体介导的,因为特异性ANG II受体拮抗剂DuP 753可消除增殖性生长。血管紧张素II还主要刺激了我们的MMC中I型胶原的生物合成。用含有与氯霉素乙酰转移酶报告基因相连的α2(I)和α1(IV)胶原增强子/启动子元件的嵌合基因转染MMC,结果表明ANG II对I型胶原的刺激作用至少在一定程度上依赖于转录的增加。这些发现共同表明,在无血清培养中,ANG II可能是系膜细胞中I型胶原生长和生物合成的旁分泌催化剂。