The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

Michael Schuliga; Jade Jaffar; Trudi Harris; Darryl A Knight; Glen Westall; Alastair G Stewart

Journal article

The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

Michael Schuliga, Jade Jaffar, Trudi Harris, Darryl A Knight, Glen Westall, Alastair G Stewart

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2017

DOI: 10.1038/srep41770

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Abstract

The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced v..

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University of Melbourne Researchers

Alastair Stewart Author Biochemistry and Pharmacology

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Grants

Awarded by NHMRC (Australia)

Funding Acknowledgements

This work was supported by the NHMRC (Australia) research grants #1022048, #1023185 and #1059665. We thank the Departments of Respiratory Medicine, Surgery, and Anatomical Pathology, Alfred Hospital, Australia, and Prof. Catriona MacClean for assistance in obtaining human lung tissue. Furthermore, we thank the Monash Histology Platform for histology preparations and Masson's trichrome staining of lung tissue. Additionally, we thank Prof Judith Black for provision of two lung fibroblast cell lines derived from IPF donors.