Zhao Y, Gilmore B J, Young S L
Research Service, Durham Veterans Affairs Medical Center, Durham, North Carolina, USA.
Am J Physiol. 1997 Aug;273(2 Pt 1):L355-62. doi: 10.1152/ajplung.1997.273.2.L355.
Lung injury and repair processes involve many cellular activities, including cell growth, differentiation, and remodeling of extracellular matrix components. Transforming growth factor-beta (TGF-beta) is a major class of signaling peptide growth factors regulating these cellular activities. Type I (T beta RI) and type II (T beta RII) receptors for TGF-beta are transmembrane serine/threonine kinases that are essential for TGF-beta signaling. To gain insight into the possible molecular mechanisms of lung injury and repair, we investigated the expression of T beta RI and T beta RII in an acute hyperoxia-induced model of lung injury and repair. Localization of message expression of T beta RI and T beta RII in oxygen-exposed rat lung tissue was analyzed by using in situ hybridization. T beta RI mRNA expression was found in the interstitium, capillaries, and the alveolar septa of rat lungs exposed for 60 h to 100% oxygen. The distribution of T beta RII mRNA in oxygen-exposed rat lung tissue overlapped the localization of T beta RI mRNA. Temporal changes of T beta RI and T beta RII mRNA expressions in rat lung during hyperoxic exposure and repair were examined by Northern analysis. We found that expression of T beta RI was upregulated in adult rats undergoing prolonged exposure to 100% oxygen, and the increase of T beta RI expression persisted during 2 wk of repair of lung injury. The pattern of T beta RII expression during hyperoxic exposure and repair was distinct from that of T beta RI. The expression of T beta RII increased with a peak at 3 days postexposure and then declined after 7 days of repair. Changes of T beta RI and T beta RII protein expressions in rat lung during hyperoxic exposure and repair were examined further by Western blot analysis, which correlated with the mRNA expression. The results suggest that T beta RI and T beta RII may play important roles during the lung injury and repair by mediating signaling activity of TGF-beta and may regulate interactions between the mesenchyme and the epithelium.
肺损伤与修复过程涉及许多细胞活动，包括细胞生长、分化以及细胞外基质成分的重塑。转化生长因子-β（TGF-β）是调节这些细胞活动的一类主要信号肽生长因子。TGF-β的Ⅰ型（TβRI）和Ⅱ型（TβRII）受体是跨膜丝氨酸/苏氨酸激酶，对TGF-β信号传导至关重要。为深入了解肺损伤与修复可能的分子机制，我们在急性高氧诱导的肺损伤与修复模型中研究了TβRI和TβRII的表达。通过原位杂交分析了TβRI和TβRII在暴露于氧气的大鼠肺组织中的信使表达定位。在暴露于100%氧气60小时的大鼠肺中，间质、毛细血管和肺泡隔中发现了TβRI mRNA表达。TβRII mRNA在暴露于氧气的大鼠肺组织中的分布与TβRI mRNA的定位重叠。通过Northern分析检测了高氧暴露和修复过程中大鼠肺中TβRI和TβRII mRNA表达的时间变化。我们发现，成年大鼠在长时间暴露于100%氧气后，TβRI表达上调，并且在肺损伤修复的2周内TβRI表达持续增加。高氧暴露和修复过程中TβRII的表达模式与TβRI不同。TβRII的表达在暴露后3天达到峰值，然后在修复7天后下降。通过蛋白质印迹分析进一步检测了高氧暴露和修复过程中大鼠肺中TβRI和TβRII蛋白表达的变化，其与mRNA表达相关。结果表明，TβRI和TβRII可能通过介导TGF-β的信号传导在肺损伤与修复过程中发挥重要作用，并可能调节间充质与上皮之间的相互作用。
