Argilés A, Ootaka T, Hill P A, Nikolic-Paterson D J, Hutchinson P, Kraft N E, Atkins R C
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Kidney Int. 1994 Jan;45(1):23-31. doi: 10.1038/ki.1994.3.
Retinoic acid (RA) is a natural derivative of vitamin A which regulates the growth and differentiation of epithelia. We have previously proposed that RA participates in compensatory kidney growth and reported that RA inhibits rat mesangial cell growth. This paper describes the effects of RA on a human renal adenocarcinoma cell line (PAD) under different growth conditions, and its interactions with epidermal growth factor (EGF). PAD cells were shown to express RA receptors alpha and beta by Northern blot analysis. In serum free cultures, addition of RA (10(-7) M) markedly increased thymidine incorporation by PAD cells (155 +/- 7% mean +/- SE vs. control in 6 separate experiments; P < 0.0001). RA also caused a significant increase in thymidine incorporation by PAD cells under conditions of rapid growth in serum supplemented medium (115 +/- 2% vs. control; P < 0.001). RA by itself was unable to reverse contact inhibition of PAD cell growth (NS vs. control), but it synergistically enhanced the mitogenic effect of EGF on confluent monolayers (110 +/- 0.6% vs. EGF alone; P < 0.05). Northern blot analysis demonstrated that PAD cells express EGF receptor mRNA, and this was not significantly modified by the addition of RA. Growth arrested (serum starved) PAD cells expressed RAR-alpha mRNA which was upregulated eightfold at three hours following the addition of 10% FCS. Thus, our data show that RA is directly mitogenic for serum starved human renal adenocarcinoma cells and that it exerts complex modulation of cell growth in the presence of EGF and serum components.
视黄酸（RA）是维生素A的天然衍生物，可调节上皮细胞的生长和分化。我们之前曾提出RA参与肾脏的代偿性生长，并报道RA可抑制大鼠系膜细胞的生长。本文描述了RA在不同生长条件下对人肾腺癌细胞系（PAD）的影响，以及它与表皮生长因子（EGF）的相互作用。通过Northern印迹分析显示，PAD细胞表达RA受体α和β。在无血清培养中，添加RA（10⁻⁷ M）可显著增加PAD细胞的胸腺嘧啶核苷掺入量（在6个独立实验中，平均±标准误为155±7%，与对照组相比；P<0.0001）。在补充血清的培养基中快速生长的条件下，RA也可使PAD细胞的胸腺嘧啶核苷掺入量显著增加（115±2%，与对照组相比；P<0.001）。RA本身无法逆转PAD细胞生长的接触抑制（与对照组相比无显著性差异），但它可协同增强EGF对汇合单层细胞的促有丝分裂作用（110±0.6%，与单独使用EGF相比；P<0.05）。Northern印迹分析表明，PAD细胞表达EGF受体mRNA，添加RA后该表达无显著改变。生长停滞（血清饥饿）的PAD细胞表达RAR-α mRNA，在添加10%胎牛血清后3小时，其表达上调了8倍。因此，我们的数据表明，RA对血清饥饿的人肾腺癌细胞具有直接促有丝分裂作用，并且在存在EGF和血清成分的情况下，它对细胞生长发挥复杂的调节作用。
