Willis Brigham C, Kim Kwang-Jin, Li Xian, Liebler Janice, Crandall Edward D, Borok Zea
Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, California 90033, USA.
Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1192-200. doi: 10.1152/ajplung.00379.2002. Epub 2003 May 2.
Transforming growth factor-beta1 (TGF-beta 1) may be a critical mediator of lung injury and subsequent remodeling during recovery. We evaluated the effects of TGF-beta 1 on the permeability and active ion transport properties of alveolar epithelial cell monolayers. Rat alveolar type II cells plated on polycarbonate filters in defined serum-free medium form confluent monolayers and acquire the phenotypic characteristics of alveolar type I cells. Exposure to TGF-beta 1 (0.1-100 pM) from day 0 resulted in a concentration- and time-dependent decrease in transepithelial resistance (Rt) and increase in short-circuit current (Isc). Apical amiloride or basolateral ouabain on day 6 inhibited Isc by 80 and 100%, respectively. Concurrent increases in expression of Na+-K+-ATPase alpha 1- and beta 1-subunits were observed in TGF-beta 1-treated monolayers. No change in the alpha-subunit of the rat epithelial sodium channel (alpha-rENaC) was seen. Exposure of confluent monolayers to TGF-beta 1 from day 4 resulted in an initial decrease in Rt within 6 h, followed by an increase in Isc over 72-96 h. These results demonstrate that TGF-beta 1 modulates ion conductance and active transport characteristics of the alveolar epithelium, associated with increased Na+-K+-ATPase, but without a change in alpha-rENaC.
转化生长因子-β1（TGF-β1）可能是肺损伤及恢复过程中后续重塑的关键介质。我们评估了TGF-β1对肺泡上皮细胞单层通透性和主动离子转运特性的影响。将大鼠II型肺泡细胞接种于聚碳酸酯滤膜上，置于特定无血清培养基中，可形成汇合的单层细胞，并获得I型肺泡细胞的表型特征。从第0天开始暴露于TGF-β1（0.1 - 100 pM）会导致跨上皮电阻（Rt）呈浓度和时间依赖性降低，短路电流（Isc）增加。第6天顶端应用阿米洛利或基底外侧应用哇巴因分别使Isc抑制80%和100%。在TGF-β1处理的单层细胞中观察到Na+-K+-ATP酶α1和β1亚基的表达同时增加。大鼠上皮钠通道（α-rENaC）的α亚基未见变化。从第4天开始将汇合的单层细胞暴露于TGF-β1，导致Rt在6小时内最初降低，随后在72 - 96小时内Isc增加。这些结果表明，TGF-β1调节肺泡上皮的离子电导和主动转运特性，这与Na+-K+-ATP酶增加有关，但α-rENaC无变化。
