Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

Tomoyuki Kakugawa,Hiroshi Ishii,Seiko Nakayama,Shigeru Kohno,Mariko Mine,Kanako Sugiyama,Noriho Sakamoto,Yohei Mizuta,Sumako Yoshioka,Tomayoshi Hayashi,Hiroshi Mukae

doi:10.1186/1465-9921-6-57

Abstract

BackgroundHeat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP).MethodsWe reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining).ResultsThe expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP.ConclusionOur results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen.

Highlights

Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases
Weak or no expression of HSP47 was noted in fibroblasts and type II pneumocytes in CVDassociated usual interstitial pneumonia (UIP) (Fig. 1H)
Patients with idiopathic UIP (P < 0.01) and idiopathic nonspecific interstitial pneumonia (NSIP) (P < 0.01) had a significantly higher expression of HSP47 in type II pneumocytes than that in control, while there was no significant difference between collagen vascular disease (CVD)-associated UIP and control

Summary

Introduction

Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. Recent reports have demonstrated that HSP47 expression is highly tissue- and cell-specific, and is restricted to most phenotypically altered collagen-producing cells, and correlates well with that of collagen [9,10,11] These findings suggest the important role of HSP47 in collagen synthesis in various fibrotic disorders. It was demonstrated that inhibition of HSP47 by antisense oligodeoxynucleotides markedly suppressed the production of collagen in 3T6 cells [4], in experimental proliferative glomerulonephritis [12] and in experimental peritoneal fibrosis [7]. These findings suggest that HSP47 might be a promising target for the treatment of fibrotic diseases

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