Department of Experimental Medical Science, BMC D12, Lund University, Lund, Sweden.
J Transl Med. 2012 Aug 22;10:171. doi: 10.1186/1479-5876-10-171.
During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment.
Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels.
The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients.
Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD.
在伤口愈合过程中，成纤维细胞通过采用收缩表型来促进伤口闭合。COPD 的一种疾病表现是肺气肿，其特征是肺泡壁的破坏，我们的假设是 COPD 肺部的成纤维细胞分化为更具收缩表型，以应对恶化的环境。
从 COPD 患者（GOLD 分期 IV）的肺组织标本（n = 9）和对照受试者的活检以及供体肺中分离支气管（中央）和肺实质（周围）成纤维细胞。通过 Western blot 评估组织来源的成纤维细胞中涉及成纤维细胞收缩的蛋白的表达，而在三维胶原凝胶中测量收缩能力。
与对照受试者的成纤维细胞相比，COPD 患者的中央和周围来源的成纤维细胞中 rho 相关卷曲螺旋蛋白激酶 1（ROCK1）的基础表达均增加（p < 0.001）和（p < 0.01）。与对照成纤维细胞相比，COPD 患者的周围来源的成纤维细胞的收缩能力增加（p < 0.01）。收缩依赖于 ROCK1 活性，因为 ROCK 抑制剂 Y27632 剂量依赖性地阻断了 COPD 患者成纤维细胞的收缩。通过免疫组织化学也在 COPD 患者的肺组织切片中的肺泡实质中鉴定了 ROCK1 阳性成纤维细胞。
COPD 患者的周围来源的成纤维细胞具有增强的收缩表型，该表型依赖于 ROCK1 活性。这一特征对于 COPD 晚期小气道和实质的弹性动力学可能很重要。
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