Mitogen-activated Protein Kinase-activated Protein Kinase 2 Inhibition Attenuates Fibroblast Invasion and Severe Lung Fibrosis.

Severe pulmonary fibrosis such as idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix and fibroblast activation. Targeting fibroblast activation has contributed to the development of antifibrotic therapeutics for patients with IPF. Mitogen-activated protein kinase-activated protein kinase 2 (MK2), downstream in the transforming growth factor-ß/p38 mitogen-activated protein kinase pathway, has been implicated in inflammatory and fibrosing diseases. Increased concentrations of activated MK2 were expressed in IPF lung and in the mouse bleomycin model of lung fibrosis. The aim of the present study was to determine the role and the mechanisms of MK2 in fibroblast invasion and lung fibrosis. Our results showed that an MK2 inhibitor (MMI-0100) was able to inhibit the invasive capacity of lung fibroblasts isolated from patients with IPF, as well as fibroblasts isolated from both wild-type mice and mice with overexpressing hyaluronan synthase 2 (HAS2) in the myofibroblast compartment. We previously showed that hyaluronan and HAS2 regulate fibroblast invasion and lung fibrosis in vivo. The results of the present study showed that MMI-0100 reduced transforming growth factor-ß-induced hyaluronan production in human and mouse fibroblasts in vitro and that HAS2 mediated MK2 activation, suggesting a feed-forward loop in fibroblast activation. More importantly, MK2 inhibition attenuated hyaluronan accumulation and reduced collagen content in bleomycin-injured mouse lungs in vivo. Conditional deletion of MK2 in fibroblasts attenuated bleomycin-induced lung fibrosis. These data provide evidence that MK2 has a role in fibroblast invasion and fibrosis and may be a novel therapeutic target in pulmonary fibrosis.

Data on the intermolecular interactions of 1,1,1,2-tetrafluoroethane liquids from molecular dynamics simulations.

Detailed atomistic interactions of 1,1,1,2-tetrafluoroethane (HFA-134a) liquid were presented in a data format, namely, DL_ANALYSER Notation for Atomic Interactions (DANAI), that annotates precisely the nature of interactions that is discoverable and searchable without having to resolve to diagrammatic illustrations. The datasets were obtained from raw atomic trajectory files of HFA-134a pure liquid models produced by using DL_POLY molecular dynamics software package. The trajectory datafiles contain expressions of atomic species in a natural chemical sense, and hence, provide localized key interactions, 'at a glance', of the liquid model on otherwise a typically disordered system consists of complex network of intermolecular interactions. The data provide insights to detailed structural behavior of molecules in liquid phase, and can be used as cheminformatics comparative investigations, linking to other molecular system models that contain similar interaction types and chemical species. This can form the foundation of investigations into the role of HFA-134a plays within different applications. For example, it can be used to compare structural and atomic interaction differences with alternative refrigerants, or as liquid propellants in pharmaceutical devices when solvating formulation ingredients.