Journal
RESPIRATORY RESEARCH
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1465-9921-10-55
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Funding
- National Natural Science Foundation of China [30425007, 30370627, 30670921]
- China Medical Board of New York [00-722, 06-834]
- Chinese Scholars from Ministry of Education, PR China
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Background: Advanced glycation end products (AGEs) have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM)-stimulated rat model treated with aminoguanidine (AG), a crosslink inhibitor of AGE formation. Methods: Rats were intratracheally instilled with BLM (5 mg/kg) and orally administered with AG ( 40, 80, 120 mg/kg) once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47), a collagen specific molecular chaperone, was measured with RTPCR and Western blot. Moreover, TGF beta 1 and its downstream Smad proteins were analyzed by Western blot. Results: AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p < 0.05). In addition, AG dose-dependently downregulated BLM-stimulated overexpressions of TGF beta 1, phosphorylated (p)-Smad2 and p-Smad3 protein in lung tissues. Conclusion: These findings suggest AGE formation may participate in the process of BLM-induced pulmonary fibrosis, and blockade of AGE formation by AG treatment attenuates BLM-induced pulmonary fibrosis in rats, which is implicated in inhibition of HSP47 expression and TGF beta/Smads signaling.
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