Attenuation of Transforming Growth Factor–β–Stimulated Collagen Production in Fibroblasts by Quercetin-Induced Heme Oxygenase–1
| Autor: | Naozumi Hashimoto, Toshinobu Nakamura, Kaoru Shimokata, Tsutomu Kawabe, Yoshinori Hasegawa, Masataka Shibasaki, Kazuyoshi Imaizumi, Yuta Hayashi, Miyoko Matsushima |
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| Rok vydání: | 2011 |
| Předmět: |
Pulmonary and Respiratory Medicine
Cytoplasm Pulmonary Fibrosis Clinical Biochemistry SMAD Lung injury Antioxidants Gene Expression Regulation Enzymologic Mice chemistry.chemical_compound Transforming Growth Factor beta medicine Animals Humans heterocyclic compounds Enzyme Inhibitors Fibroblast Molecular Biology Transcription factor Cell Nucleus Chemistry Cell Biology Fibroblasts Immunohistochemistry Cell biology Heme oxygenase medicine.anatomical_structure Biochemistry NIH 3T3 Cells Quercetin Collagen Signal transduction Heme Oxygenase-1 Transforming growth factor |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 44:614-620 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2010-0338oc |
| Popis: | Quercetin is a flavonoid with a wide variety of cytoprotective and modulatory functions. Heme oxygenase-1 (HO-1) is an inducible enzyme. Its reaction product, carbon monoxide (CO), confers cellular protection in a number of conditions and diseases associated with oxidative or inflammatory lung injury. Furthermore, quercetin was reported to be a potent inducer of HO-1 in several cell types. We hypothesized that quercetin suppresses the production of collagen in fibroblasts via the induction of HO-1. Here, we showed that quercetin suppresses transforming growth factor-β (TGF-β)-induced collagen production in NIH3T3 cells and in normal human lung fibroblasts. This suppressive effect of quercetin was mediated by quercetin-induced HO-1. The suppression of collagen production was conferred by the reaction product of HO-1, CO, but not by bilirubin. Furthermore, the translocation of the nuclear factor E2-related factor-2 (Nrf2), an important transcription factor that regulates the expression of HO-1 from the cytoplasm to the nuclei, was demonstrated in NIH3T3 cells by exposure to quercetin. Assessment of the signal transduction pathway involved in TGF-β signaling showed that quercetin stimulated the Smad and mitogen-activated protein kinase pathway to varying degrees. Our results demonstrate that quercetin exerts suppressive effects on the expression of collagen by the induction of HO-1. Idiopathic pulmonary fibrosis is the most lethal diffuse fibrosing lung disease, and is characterized by the deposition of extracellular matrix. Given that HO-1 is one of the important molecules emerging as a central player in diseases, quercetin or its derivatives, which effectively induced HO-1, will lead to new therapeutic strategies for promoting antifibrotic therapy in respiratory diseases. |
| Databáze: | OpenAIRE |
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