Functional analysis of tetraspanins(CD9, CD151) in lung fibrosis

肺纤维化(PF)是过量的纤维结缔组织形成的过程，其特征是纤维性胶原的堆积。Tetraspanins是整合素的关键伙伴，促进多个分子复合体的形成，调节细胞功能。我们先前报道了Tetraspanin CD9和CD81双缺失在自发发展为COPD样表型的小鼠中的作用。来自DNA微阵列的基因功能分析出人意料地显示，在CD151 KO肺中，结缔组织的发育和功能排名很高。值得注意的是，CD151KO小鼠随着年龄的增长自发地发展为肺纤维化。在CD151KO小鼠中，p-Smad2在全肺和上皮细胞中的水平一直升高。事实上，肺泡上皮细胞中CD151的缺失导致Matrigel上p-Smad2活性增加，并导致间充质样变。有趣的是，与健康对照组相比，IPF患者上皮细胞中CD151的表达下调。鉴于CD151通过维持上皮完整性在预防纤维化中起着关键作用，CD151可能成为PF的新靶点。

Pulmonary fibrosis(PF) is the process whereby excess fibrous connective tissue forms and characterized by the accumulation of fibrillar collagen. Tetraspanins, key partners of integrins, facilitate the formation of multiple molecular complexes and regulate cell function. We previously reported double deletion of tetraspanin CD9 and CD81 in mice spontaneously developed COPD-like phenotype. The gene functions analyses from DNA Microarray unexpectedly revealed that' connective tissue development and function' were ranked high in CD151 KO lungs. Notably, CD151 KO mice spontaneously developed lung fibrosis with age. Consistently, the level of p-Smad2 in the CD151 KO mice was augmented in the whole lung and in the epithelium. Indeed, deletion of CD151 in alveolar epithelial cells leads to increased p-Smad2 activity on Matrigel, and mesenchymal-like changes. Of interest, expression of CD151 in epithelial cells from IPF patients was downregulated compared with that of healthy controls. Given that CD151 plays a pivotal role to prevent fibrosis through maintaining epithelial integrity, CD151 could be a novel target for PF.