Modulation of ion conductance and active transport by TGF-β1 in alveolar epithelial cell monolayers
Modulation of ion conductance and active transport by TGF-β1 in alveolar epithelial cell monolayers
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DOI：
10.1152/ajplung.00379.2002
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发表时间：
2003-12-01
影响因子：
4.9
通讯作者：
Borok, Z
中科院分区：
文献类型：
--
作者：
Willis, BC;Kim, KJ;Borok, Z
转化生长因子-β 1（TGF-β 1）可能是恢复期间肺损伤和随后重塑的关键介质。我们评估了TGF-β 1对肺泡上皮细胞单层的渗透性和活性离子转运特性的影响。大鼠肺泡II型细胞接种在聚碳酸酯过滤器上，在确定的无血清培养基中形成融合单层，并获得肺泡I型细胞的表型特征。从第0天开始暴露于TGF-β 1（0.1 - 100 pM）导致跨上皮电阻（R-t）呈浓度和时间依赖性降低，短路电流（I-sc）增加。阿米洛利或基底外侧哇巴因在第6天分别抑制了80%和100%的Isc。在TGF-β 1处理的单层细胞中观察到Na+- K+-ATP酶α（1）-和β（1）-亚基表达的同时增加。未观察到大鼠上皮钠通道（alpha-rENaC）的α亚单位发生变化。从第4天开始，将融合单层细胞暴露于TGF-β 1导致Rt在6 h内初始降低，随后在72 - 96 h内Isc增加。这些结果表明，TGF-β 1调节离子传导和肺泡上皮细胞的主动运输特性，与增加Na+-K+-ATP酶，但没有改变α-rENaC。
Transforming growth factor-beta1 (TGF-beta1) may be a critical mediator of lung injury and subsequent remodeling during recovery. We evaluated the effects of TGF-beta1 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-beta1 (0.1 - 100 pM) from day 0 resulted in a concentration- and time-dependent decrease in transepithelial resistance (R-t) and increase in short-circuit current (I-sc). 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-beta1-treated monolayers. No change in the alpha-subunit of the rat epithelial sodium channel (alpha-rENaC) was seen. Exposure of confluent monolayers to TGF-beta1 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-beta1 modulates ion conductance and active transport characteristics of the alveolar epithelium, associated with increased Na+-K+-ATPase, but without a change in alpha-rENaC.