scholarly journals P2‐27: Identification of inhibitors targeting heat shock protein 47 for the development of anti‐fibrotic therapeutics

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 123-124
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 47

Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy

2003 ◽  
Vol 285 (4) ◽  
pp. L957-L963 ◽  
Author(s):  
Hiroshi Ishii ◽  
Hiroshi Mukae ◽  
Tomoyuki Kakugawa ◽  
Tetsuji Iwashita ◽  
Hideyuki Kaida ◽  
...  
Keyword(s):  
Heat Shock ◽  
Pulmonary Fibrosis ◽  
Heat Shock Protein ◽  
Smooth Muscle Actin ◽  
Protein A ◽  
Immunohistochemical Analysis ◽  
Rt Pcr ◽  
Heat Shock Protein 47 ◽  
Positive Type ◽  
Fibrotic Process

The 47-kDa heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen. Expression of HSP47 has been reported to increase in parallel with expression of collagens during the progression of various fibrosis models. The aim of the present study was to investigate the association between HSP47 expression and collagen accumulation in bleomycin (BLM)-induced murine fibrosis. We investigated the expression of HSP47 protein and mRNA using immunohistochemical analysis and semi-quantitative RT-PCR in murine BLM-induced pulmonary fibrosis. Immunohistochemical analysis showed that higher expression of HSP47 protein was present in BLM-induced pulmonary fibrosis compared with controls. HSP47 was localized predominantly in α-smooth muscle actin-positive myofibroblasts, F4/80 negative, surfactant protein-A-positive type II pneumocytes, and F4/80-positive macrophages. RT-PCR also demonstrated an increase of HSP47 mRNA expression in BLM-treated lungs. Moreover, the relative amounts of HSP47 mRNA correlated significantly with the lung hydroxyproline content as an indicator of pulmonary fibrosis in BLM-treated lungs ( r = 0.406, P <0.05). Our results suggest that these cells may play a role in the fibrotic process of BLM-treated lungs through upregulation of HSP47.

Heat Shock Protein 47 (HSP47)

2018 ◽  
pp. 1-7
Author(s):  
Fatin Hazwani Ibrahim ◽  
Normala Abd Latip ◽  
Mohd Firdaus Abdul-Wahab
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 47

Rapid Fibroblast Cell Culture Characterization with Impedimetric Label‐free Heat Shock Protein – 47 Biosensor

2020 ◽  
Vol 32 (10) ◽  
pp. 2310-2315
Author(s):  
Duygu Harmanci ◽  
Zihni Onur Uygun ◽  
Ayşe Koçak Sezgin ◽  
Cenk Demirdöver ◽  
Ferhan Girgin Sagin ◽  
...  
Keyword(s):  
Cell Culture ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Fibroblast Cell ◽  
Label Free ◽  
Heat Shock Protein 47 ◽  
Fibroblast Cell Culture

Heat Shock Protein 47: A New Platelet Collagen Receptor

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 158-158
Author(s):  
William J Kaiser ◽  
Tanya Sage ◽  
Parvathy Sasikumar ◽  
Frederick Kemp ◽  
Nicholas Pugh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Small Molecule ◽  
Platelet Function ◽  
Small Molecule Inhibitor ◽  
Collagen Fibrils ◽  
Platelet Surface ◽  
Heat Shock Protein 47 ◽  
Molecule Inhibitor ◽  
Collagen Receptor

Abstract Abstract 158 We recently reported that Heat shock protein 47 (Hsp47), a well established collagen binding protein, was present on the surface of human platelets. In the current study we demonstrate that anti-Hsp47 antibodies and a small molecule inhibitor of Hsp47 selectively prevent aggregation of platelets induced with collagen fibrils. Inhibition of Hsp47 was also found to reduce the size of thrombi produced upon perfusion of blood under arterial flow conditions over collagen in vitro. Inclusion of Integrilin, to prevent platelet-platelet interactions via fibrinogen, indicated that the reduced size of thrombi was due to fewer direct platelet-collagen interactions. Collagen-induced tyrosine phosphorylation of Syk, an early marker of signalling from the collagen receptor GPVI was unaffected by the Hsp47 inhibitor, suggesting that any contribution to platelet function by Hsp47 may be independent of GPVI-proximal signalling. Surface plasmon resonance analysis of recombinant his-tagged human Hsp47 revealed its ability to interact directly with collagen fibrils, an interaction that was disrupted by the small molecule inhibitor of Hsp47. Mouse platelets were also found to contain Hsp47, and aggregation induced with collagen was reduced by inhibitors of Hsp47. Infusion of Hsp47 inhibitor into mice increased tail bleeding times and volumes of blood lost, even in the absence of anticoagulant. This effect was likely due to inhibition of platelet function, since the thrombi formed in cremaster muscle arterioles using an intravital laser-injury model of thrombosis were smaller following administration of the Hsp47 inhibitor. Together these data indicate Hsp47 to function on the platelet surface as a collagen receptor that potentially represents a new target for antithrombotic therapy. Disclosures: No relevant conflicts of interest to declare.

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