Razzaque M S, Nazneen A, Taguchi T
Second Department of Pathology, Nagasaki University School of Medicine, Sakamoto, Japan.
Mod Pathol. 1998 Dec;11(12):1183-8.
Pulmonary fibrosis resulting from increased accumulation of various extracellular matrices is a prominent feature in chronic progressive lung diseases. Heat shock protein 47 (HSP47) is a collagen-binding stress protein known to have a specific role in the intracellular processing of procollagen molecules as a collagen-specific molecular chaperone in various organs. Possible involvement, however, of HSP47 in relation to increased deposition of collagens in fibrotic lung diseases is not yet known. In this study, we investigated the expression of HSP47 in various pulmonary fibrotic diseases. Formalin-fixed, paraffin-embedded lung sections from 17 autopsies of patients with various pulmonary fibrotic diseases, e.g., organizing pneumonia, interstitial pneumonia, idiopathic pulmonary fibrosis, and diffuse alveolar damage, were stained with monoclonal antibodies for alpha-smooth muscle actin, vimentin, CD68, Type III collagen, and HSP47. The extent of staining was graded semiquantitatively. Five control lung sections were also simultaneously studied. The fibrotic lung sections, in comparison with the control sections, had more interstitial cells positive for alpha-smooth muscle actin and fibroblasts positive for vimentin; we also saw increased infiltration of CD68-positive macrophages. For HSP47, in comparison with the control lung sections, markedly increased immunostaining was always noted in the fibrotic lung sections in association with increased accumulation of Type III collagen in the fibrotic masses. By double immunostaining, colocalization of collagens and HSP47 was noted in the regions of pulmonary fibrosis, and HSP47-expressing cells were found to be mainly alpha-smooth muscle actin-positive interstitial cells. From the above observations, we concluded that overexpression of HSP47 might play an important role in the excessive assembly/synthesis of collagens and could thereby contribute to the fibrosis found in pulmonary fibrotic lung diseases.
各种细胞外基质积累增加导致的肺纤维化是慢性进行性肺病的一个显著特征。热休克蛋白47（HSP47）是一种胶原结合应激蛋白，作为各种器官中胶原特异性分子伴侣，已知其在原胶原分子的细胞内加工过程中发挥特定作用。然而，HSP47与纤维化肺病中胶原沉积增加的关系尚不清楚。在本研究中，我们调查了HSP47在各种肺纤维化疾病中的表达。对17例各种肺纤维化疾病患者（如机化性肺炎、间质性肺炎、特发性肺纤维化和弥漫性肺泡损伤）尸检获得的福尔马林固定、石蜡包埋肺切片，用抗α-平滑肌肌动蛋白、波形蛋白、CD68、III型胶原和HSP47的单克隆抗体进行染色。染色程度进行半定量分级。同时也对5个对照肺切片进行了研究。与对照切片相比，纤维化肺切片中有更多α-平滑肌肌动蛋白阳性的间质细胞和波形蛋白阳性的成纤维细胞；我们还观察到CD68阳性巨噬细胞浸润增加。对于HSP47，与对照肺切片相比，纤维化肺切片中总是观察到免疫染色明显增加，且与纤维化灶中III型胶原积累增加有关。通过双重免疫染色，在肺纤维化区域发现胶原与HSP47共定位，且发现表达HSP47的细胞主要是α-平滑肌肌动蛋白阳性的间质细胞。根据上述观察结果，我们得出结论，HSP47的过表达可能在胶原的过度组装/合成中起重要作用，从而可能导致肺纤维化疾病中的纤维化。
