Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis.

Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2019 Sep 04;: Authors: Xylourgidis N, Min K, Ahangari F, Yu G, Herazo-Maya JD, Karampitsakos T, Aidinis V, Binzenhöfer L, Bennett AM, Kaminski N, Tzouvelekis A Abstract Mitogen-activated protein kinase (MAPK) phosphatase-5 (MKP-5), is a member of the dual-specificity family of protein tyrosine phosphatases, which negatively regulates p38 MAPK and the c-Jun NH2 kinase (JNK). MKP-5-deficient mice exhibit improved muscle repair and reduced fibrosis in an animal model of muscular dystrophy. Here, we asked whether the effects of MKP-5 on muscle fibrosis extends to other tissues. Using a bleomycin-induced model of pulmonary fibrosis, we found that MKP-5-deficient mice were protected from the development of lung fibrosis and expressed reduced levels of hydroxyproline and fibrogenic genes and a marked polarization towards an M1- macrophage phenotype. We show that the pro-fibrogenic effects of the transforming growth factor-beta1 (TGF-b1) are inhibited in MKP-5-deficient lung fibroblasts. MKP-5-deficient fibroblasts exhibited enhanced p38 MAPK activity, impaired Smad3 phosphorylation, increased Smad7 levels and decreased expression of fibrogenic genes. Myofibroblast differentiation was attenuated in MKP-5-deficient fibroblasts. Finally, we found that MKP-5 expression was increased in idiopathic pulmonary fibrosis (IPF)-deriv...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research