Journal article

Cellular Microenvironment Stiffness Regulates Eicosanoid Production and Signaling Pathways

Asres Berhan, Trudi Harris, Jade Jaffar, Fernando Jativa, Shenna Langenbach, Ingrid Loennstedt, Monther Alhamdoosh, Milica Ng, Peter Lee, Glen Westall, Nick Wilson, Michael Wilson, Alastair G Stewart

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | AMER THORACIC SOC | Published : 2020

Abstract

Pathological changes in the biomechanical environment are implicated in the progression of idiopathic pulmonary fibrosis (IPF). Stiffened matrix augments fibroblast proliferation and differentiation and activates TGF-β1 (transforming growth factor-β1). Stiffened matrix impairs the synthesis of the antifibrogenic lipid mediator prostaglandin E2 (PGE2) and reduces the expression of the rate-limiting prostanoid biosynthetic enzyme cyclooxygenase-2 (COX-2). We now show that prostaglandin E synthase (PTGES), the final enzyme in the PGE2 biosynthetic pathway, is expressed at lower levels in the lungs of patients with IPF. We also show substantial induction of COX-2, PTGES, prostaglandin E receptor..

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Grants

Awarded by Australian Research Council


Awarded by National Health and Medical Research Council (Australia) Centre for Research Excellence in Pulmonary Fibrosis


Awarded by Ideas grant


Funding Acknowledgements

Supported by grants from the Australian Research Council (IC170100016 and LP160100635) and the National Health and Medical Research Council (Australia) Centre for Research Excellence in Pulmonary Fibrosis (1116371), Ideas grant 1181637, and CSL Ltd.