title: ROCK activation in lung of idiopathic pulmonary fibrosis with oxidative stress.
abstract: The Rho-associated coiled-coil containing protein kinase, (Rho-kinase or ROCK) undergoes activation by oxidative stress. ROCK-II, which is an isoform of ROCK, is activated in a murine model of lung fibrosis. The present study evaluated the level of oxidative stress and activation of ROCK-II in patients with idiopathic pulmonary fibrosis (IPF). The ROCK-II level and the phosphorylation of myosin phosphatase subunit-1 (p-MYPT-1), a hallmark of ROCK activation, were examined by immunohistochemistry of lung tissue sections. The 8-iso prostaglandin-F2alpha (8-isoPGF2alpha) level, as a marker of oxidative stress, of exhaled breath condensate was significantly higher in IPF patients than in control patients. In IPF lungs, ROCK-II was predominantly expressed by bronchial epithelial cells, as well as at a lower level by airway smooth muscle cells, vascular smooth muscle cells, and the fibroblasts of fibroblastic foci (FF). In addition, there was moderate p-MYPT-1 expression in these cells of IPF lungs. In control lungs, ROCK-II was expressed by these cells. p-MYPT-1 was weakly expressed by the bronchial epithelial cells. In conclusion, ROCK-II was activated in various lung cells of IPF patients along with oxidative stress detected by 8-isoPGF2alpha elevation. The ROCK pathway may play a role in the development of IPF oxidative stress.
authors.affiliation: Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Gunma University Faculty of Health Science, Maebashi, Gunma, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Dobashi
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sano
authors.affiliation: Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: D001944:Breath Tests; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D018384:Oxidative Stress; D054460:rho-Associated Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human