Nowak G, Schnellmann R G
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Am J Physiol. 1996 Sep;271(3 Pt 2):F689-97. doi: 10.1152/ajprenal.1996.271.3.F689.
Transforming growth factor-beta 1 (TGF-beta 1) treatment (0.2-2.0 ng/ml, 8-80 M) of confluent primary cultures of rabbit renal proximal bular cells (RPTC) for 6 consecutive days resulted in both a benotypic transformation of the monolayer into solid clus- rs of cells and apoptosis. TGF-beta 1 treatment stimulated glycolysis before any effect on monolayer DNA content or morphology. TGF-beta 1 treatment also resulted in a 35% decrease in oxygen consumption, 50% inhibition of Na(+)-K(+)- ATPase activity, and a 57% decrease in gluconeogenesis. A concentration of 0.06 ng/ml TGF-beta 1 decreased oxygen consumption and induced glycolysis but had no effect on morphology and viability of RPTC. Endogenous production of TGF-beta 1 by RPTC increased 2.6-fold during 10 days of culture. Control RPTC treated with anti-TGF-beta antibodies exhibited decreased glycolysis, and lactate metabolism shifted from net production to net consumption. These results show that TGF-beta 1 stimulates glycolysis, decreases respiration, and, at higher concentrations, induces RPTC apoptosis and phenopic changes. Inhibition of net lactate production in cells grown in the presence of anti-TGF-beta antibodies suggests that increased endogenous production of TGF-beta is responsible for the stimulation of glycolysis in long-term cultures of RPTC.
用转化生长因子-β1（TGF-β1）（0.2 - 2.0纳克/毫升，8 - 80微摩尔）连续6天处理汇合的兔肾近端小管细胞（RPTC）原代培养物，导致单层细胞发生表型转化，形成细胞的坚实聚集体，并引发细胞凋亡。在对单层细胞的DNA含量或形态产生任何影响之前，TGF-β1处理就刺激了糖酵解。TGF-β1处理还导致耗氧量降低35%，钠钾ATP酶活性抑制50%，糖异生减少57%。浓度为0.06纳克/毫升的TGF-β1降低了耗氧量并诱导了糖酵解，但对RPTC的形态和活力没有影响。在培养10天期间，RPTC内源性TGF-β1的产生增加了2.6倍。用抗TGF-β抗体处理的对照RPTC显示糖酵解减少，乳酸代谢从净产生转变为净消耗。这些结果表明，TGF-β1刺激糖酵解，降低呼吸作用，并且在较高浓度下诱导RPTC凋亡和表型变化。在抗TGF-β抗体存在下生长的细胞中净乳酸产生的抑制表明，内源性TGF-β产生的增加是RPTC长期培养中糖酵解刺激的原因。
