Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury

Smith, Monica R.; Gangireddy, Srinivasa R.; Narala, Venkata Ramireddy; Hogaboam, Cory M.; Standiford, Theodore J.; Christensen, Paul J.; Kondapi, Anand K.; Reddy, Raju C.

doi:10.1152/ajplung.00002.2009

Cited by 94 publications

(92 citation statements)

References 42 publications

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“…The dose of curcumin used by us was based on its optimal anti-TGF-␤ effects at 5 mg/kg body wt in our preliminary experiments with 2.5, 5, and 20 mg/kg body wt. This dose is markedly lower than those used in adults by others, either by the oral or parenteral route (10,29). Our investigation into the mechanism of curcumin's protective effect on neonatal lung injury suggests blockage of hyperoxia-induced oxidative stress and TGF-␤ activation.…”

Section: Discussionmentioning

confidence: 64%

“…However, it is important to point out that a number of studies have stressed the limited bioavailability of oral curcumin, thereby necessitating parenteral administration to achieve its effects (13,27,29). Therefore, we opted for the intraperitoneal route over the oral route for its administration.…”

Section: Discussionmentioning

confidence: 99%

“…Our investigation into the mechanism of curcumin's protective effect on neonatal lung injury suggests blockage of hyperoxia-induced oxidative stress and TGF-␤ activation. Similarly, curcumin has been shown to inhibit bleomycininduced pulmonary fibrosis by modulating TGF-␤ signaling (4,29). In the same vein, curcumin has been shown to counteract TGF-␤-mediated downregulation of PPAR␥ in hepatic stellate cells, which are the liver equivalent of AIFs (39).…”

Section: Discussionmentioning

confidence: 99%

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Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Sakurai

Torday

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Curcumin has potent antioxidant and anti-inflammatory properties, and it modulates signaling of peroxisome proliferator-activated receptor-␥ (PPAR␥), an important molecule in the pathobiology of BPD. However, its role in the prevention of BPD is not known. We determined 1) if curcumin enhances neonatal lung maturation, 2) if curcumin protects against hyperoxia-induced neonatal lung injury, and 3) if this protection is mediated by blocking TGF-␤. Embryonic day 19 fetal rat lung fibroblasts were exposed to 21% or 95% O 2 for 24 h following 1 h of treatment with curcumin. Curcumin dose dependently accelerated e19 fibroblast differentiation [increased parathyroid hormone-related protein (PTHrP) receptor, PPAR␥, and adipocyte differentiation-related protein (ADRP) levels and triolein uptake] and proliferation (increased thymidine incorporation). Pretreatment with curcumin blocked the hyperoxia-induced decrease (PPAR␥ and ADRP) and increase (␣-smooth muscle actin and fibronectin) in markers of lung injury/repair, as well as the activation of TGF-␤ signaling. In a separate set of experiments, neonatal Sprague-Dawley rat pups were exposed to 21% or 95% O 2 for 7 days with or without intraperitoneal administration of curcumin. Analysis for markers of lung injury/repair [PTHrP receptor, PPAR␥, ADRP, fibronectin, TGF-␤ receptor (activin receptor-like kinase 5), and Smad3] and lung morphology (radial alveolar count) demonstrated that curcumin effectively blocks TGF-␤ activation and hyperoxia-induced lung injury. Therefore, curcumin accelerates lung maturation by stimulating key alveolar epithelial-mesenchymal interactions and prevents hyperoxiainduced neonatal lung injury, possibly by blocking TGF-␤ activation, suggesting that it is a potential intervention against BPD. bronchopulmonary dysplasia; hyperoxia; transforming growth factor-␤ APPROXIMATELY 30% of premature infants with birth weights Ͻ1,000 g develop bronchopulmonary dysplasia (BPD) (15). The "new" BPD is characterized by abnormal lung cytoarchitecture, characterized by deranged alveolarization, with minimal large and small airway changes, and relatively mild inflammation and fibrosis (9). Infants with BPD are at significant risk of increased morbidity and mortality. They are unable to oxygenate efficiently and often require O 2 supplementation well into childhood. Although the pathogenesis of BPD is not completely understood, hyperoxia, inflammation, and/or ventilator exposure of the premature lung are the principal causative factors (33). More importantly, there is no effective intervention to prevent or treat BPD (3).Mesenchymal interstitial fibroblasts play an important role in lung development and injury/repair (16,34,36,38). During lung development and injury/repair, alveolar interstitial fibroblasts (AIFs) differentiate into lipid-laden AIFs (lipofibroblasts), which promote alveolar epithelial cell proliferation and differentiation (36). However, if AIFs lose their lipogenic phenotype and transdifferentiate to a myogenic phenotype, i.e., myofibroblasts, the...

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Sakurai

Torday

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Most of the reports pay more attention to the anti-fibrosis activity of curcumin on TGF-β1-stimulated organs (Tubulointerstitial, corneal, liver, etc.) fibrosis via blocking TGF-β signing pathway (Smith et al, 2010;Yao et al, 2012;Zhang et al, 2012). Kim et al have confirmed that curcumin inhibites TGF-β1-induced MMPs in mouse keratinocytes (Santibáñez et al, 2000;Santibáñez et al, 2002), but the effects on breast cancer MDA-MB -231 have not been reported.…”

Section: Introductionmentioning

confidence: 97%

Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells

Mo¹,

Li²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Studies of human gingival fibroblasts, lung fibroblasts, hepatic stellate cells, synoviocytes and cell lines from various malignant tumors demonstrated that curcumin inhibits cell proliferation and induces apoptosis (Jiang et al, 1996;Atsumi et al, 2006;Chen et al, 2006;Divya and Pillai, 2006;Jackson et al, 2006;Lin et al, 2009;Montopoli et al, 2009;Smith et al, 2010;Wu et al, 2010;Liu et al, 2011). The mechanisms implicated in curcumin-induced apoptosis appear to be DOI:http://dx.doi.org/10.7314/APJCP.2012.13.1.289 Antifibrotic Effect of Curcumin in TGF-β1-Induced Myofibroblasts from Human Oral Mucosa multifactorial, including effect on the stability of p53, the release of cytochrome c from mitochondria, and the generation of ROS (Strimpakos and Sharma, 2008).…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Effect of Curcumin in TGF-β1-Induced Myofibroblasts from Human Oral Mucosa

Zhang

Gong

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Asian Pacific J Cancer Prev, 13, 289-294 IntroductionOral submucous fibrosis (OSF) is a chronic inflammatory disease, and has been defined by WHO as one of the precancerous conditions (International Agency for Research on Cancer, 2005). The main clinical symptoms include the stiffness of oral mucosa, restriction of mouth opening, atrophy of tongue papillae, blisters, and intolerance to hot and spicy food. Malignant transformation rate in OSF is high, reaching 7-13% (Tilakaratne et al., 2006). The disease exhibits characteristic histological features of excessive collagen deposition in the lamina propria, following the epithelium becomes atrophic (Singh et al., 2010).OSF is closely associated with betel quid (BQ) chewing, a habit common in South and Southeast Asia, some parts of Africa, and among immigrants from these regions (Boucher and Mannan, 2002). An imbalance in collagen synthesis and degradation in oral mucosa is generally believed to be the main cause of OSF;The disease is considered a type of collagen metabolism disorder (Rajalalitha and Vali, 2005).Myofibroblasts are typically activated fibroblasts, although they can also be derived from other cell types, including epithelial and endothelial cells via epithelial/ endothelial mesenchymal transition (EMT/EndMT) process, as well as from the circulating fibroblast-like cells AbstractBackground: Myofibroblasts play an important role in the development of oral submucous fibrosis (OSF). In the current study, we investigate the effect of curcumin on growth and apoptosis of myofibroblasts derived from human oral mucosa. Methods: Myofibroblasts were generated by incubating fibroblasts, obtained from human oral mucosa, with transforming growth factor-β1 (TGF-β1). MTT, PI staining, and FACS assays were used to investigate curcumin's effect on proliferation and cell cycle of fibroblasts and myofibroblasts. Annexin V/PI binding and FACS assays were used to examine apoptosis of myofibroblasts, Western blotting to determine the levels of Bcl-2 and Bax, and enzyme-linked immunosorbant assay was employed to examine the levels of collagen type I and III in the supernatants of myofibroblasts. Results: Curcumin inhibits proliferation of fibroblasts and myofibroblasts; it also disturbs the cell cycle, induces apoptosis and decreases the generation of collagen type I and III in myofibroblasts, which are more sensitive to its effects than fibroblasts. Curcumin induces apoptosis in myofibroblasts by down-regulating the Bcl-2/ Bax ratio. Conclusion: Our results demonstrate the antifibrotic effect of curcumin in vitro. It may therefore be a candidate for the treatment of OSF.

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Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury

Cited by 94 publications

References 42 publications

Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells

Antifibrotic Effect of Curcumin in TGF-β1-Induced Myofibroblasts from Human Oral Mucosa

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