| Angiotensin II plays a critical role in diabetic pulmonary fibrosis most likely via activation of NADPH oxidase-mediated nitrosative damage. | |
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MedLine Citation:
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PMID: 21487074 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Diabetic patients have a high risk of pulmonary disorders that are usually associated with restrictive impairment of lung function, suggesting a fibrotic process (van den Borst et al. Chest 138: 393-406, 2010; Ehrlich et al. Diabetes Care 33:55-60, 2010). The present study was undertaken to define whether and how diabetes causes lung fibrosis. Lung samples from streptozotocin-induced type 1 diabetic mice, spontaneously developed type 1 diabetic OVE26 mice, and their age-matched controls, were investigated with histopathological and biochemical analysis. Signaling mechanism was investigated with cultured normal human lung fibroblasts in vitro. In both diabetes models, histological examination with Sirius-red and H & E stains showed fibrosis, along with massive inflammatory cell infiltration. The fibrotic and inflammatory processes were confirmed by real time PCR and Western blotting assays for the increased fibronectin, CTGF, PAI-1 and TNF-α mRNA and protein expressions. Diabetes also significantly increased NADPH oxidase (NOX) expression and protein nitration, along with up-regulation of angiotensin II (Ang II) and its receptor expression. In cell culture, exposure of lung fibroblasts to Ang II increased CTGF expression in a dose- and time-dependent manner, which could be abolished by inhibition of superoxide, NO, and peroxynitrite accumulation. Furthermore, chronic infusion of Ang II to normal mice at a subpressor dose induced diabetes-like lung fibrosis, and Ang II receptor AT1 blocker (losartan) abolished the lung fibrotic and inflammatory responses in diabetic mice. These results suggest that Ang II plays a critical role in diabetic lung fibrosis, which is most likely caused by NOX activation-mediated nitrosative damage. |
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Authors:
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Juling Yang; Yi Tan; Fenglian Zhao; Zhongsen Ma; Yuehui Wang; Shirong Zheng; Paul N Epstein; Jerry Yu; Xia Yin; Yang Zheng; Xiaokun Li; Li-Ning Miao; Lu Cai |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-12 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: - ISSN: 1522-1555 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Jilin University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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