Transforming growth factor-beta 1 regulation of signal transduction in two renal epithelial cell lines.
Transforming growth factor-beta 1 regulation of signal transduction in two renal epithelial cell lines.
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转化生长因子-β1 对两种肾上皮细胞系信号转导的调节。
DOI：
10.1152/ajprenal.1993.265.4.f584
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Hoeffler,JP
中科院分区：
文献类型：
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作者：
Anderson,RJ;Sponsel,HT;Breckon,R;Marcell,T;Hoeffler,JP
本研究检测了转化生长因子β 1（TGF-β 1）对两种培养的肾上皮细胞系信号转导通路的影响。TGF-β 1促进LLC-PK 1细胞膜中基础和激动剂刺激的腺苷酸环化酶活性，但不促进MDCK细胞膜。TGF-β 1对LLC-PK 1膜腺苷酸环化酶活性的刺激发生迅速，并且可以通过百日咳毒素预处理减弱。TGF-β 1和环磷酸腺苷（cAMP）对LLC-PK 1细胞中[3 H]胸苷摄取的影响相当，表明TGF-β 1对腺苷酸环化酶活性的调节可能在介导对TGF-β 1的生物反应中发挥作用。蛋白激酶C和磷脂酶A的活性不受LLC-PK 1或MDCK细胞中TGF-β 1的影响。TGF-β 1和表皮生长因子（EGF）均增加LLC-PK 1细胞中cAMP反应元件结合蛋白（CREB）的表达并诱导其出现新形式。TGF-β 1和EGF对CREB的这些作用似乎是特异性的，因为TGF-β 1和EGF都不改变LLC-PK 1细胞中激活转录因子的表达。TGF-β 1和EGF改变CREB表达的作用不影响CREB与LLC-PK 1细胞裂解物中其调节元件的结合。这些结果表明，TGF-β 1的一些生物学效应可能归因于腺苷酸环化酶活性和cAMP形成的刺激，以及LLC-PK 1细胞中CREB转录因子的表达增强和/或修饰。
The present studies examine the effect of transforming growth factor-beta 1 (TGF-beta 1) on signal transduction pathways in two cultured renal epithelial cell lines. TGF-beta 1 promotes basal and agonist-stimulated adenylate cyclase activity in LLC-PK1 but not MDCK cell membranes. TGF-beta 1 stimulation of LLC-PK1 membrane adenylate cyclase activity occurs quickly and can be attenuated by pertussis toxin pretreatment. Both TGF-beta 1 and adenosine 3',5'-cyclic monophosphate (cAMP) exert comparable effects on [3H]thymidine uptake in LLC-PK1 cells, suggesting that TGF-beta 1 regulation of adenylate cyclase activity potentially plays a role in mediating biological responses to TGF-beta 1. The activities of protein kinase C and phospholipase A are not affected by TGF-beta 1 in either LLC-PK1 or MDCK cells. Both TGF-beta 1 and epidermal growth factor (EGF) increase expression and induce the appearance of new forms of the cAMP response element binding protein (CREB) in LLC-PK1 cells. These effects of TGF-beta 1 and EGF on CREB appear to be specific since neither TGF-beta 1 nor EGF alters expression of an activating transcription factor in LLC-PK1 cells. The effect of TGF-beta 1 and EGF to alter expression of CREB does not affect CREB binding to its regulatory element in LLC-PK1 cell lysates. These results suggest that some of the biological effects of TGF-beta 1 may be attributed to stimulation of adenylate cyclase activity and cAMP formation as well as to enhanced expression and/or modification of the CREB transcription factor in LLC-PK1 cells.