Curcumin differentially regulates TGF-β1, its receptors and nitric oxide synthase during impaired wound healing

BioFactors ◽  
2002 ◽  
Vol 16 (1-2) ◽  
pp. 29-43 ◽  
Author(s):  
Haresh Mani ◽  
Gurmel S. Sidhu ◽  
Ranjana Kumari ◽  
Jaya P. Gaddipati ◽  
Pankaj Seth ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Nitric Oxide Synthase ◽  
Impaired Wound Healing ◽  
Oxide Synthase ◽  
Tgf Β1

Nitric oxide attenuates epithelial-mesenchymal transition in alveolar epithelial cells

2007 ◽  
Vol 293 (1) ◽  
pp. L212-L221 ◽  
Author(s):  
Shilpa Vyas-Read ◽  
Philip W. Shaul ◽  
Ivan S. Yuhanna ◽  
Brigham C. Willis
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Epithelial Cells ◽  
No Production ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Oxide Synthase ◽  
Tgf Β1

Patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF) and bronchopulmonary dysplasia (BPD), suffer from lung fibrosis secondary to myofibroblast-mediated excessive ECM deposition and destruction of lung architecture. Transforming growth factor (TGF)-β1 induces epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) to myofibroblasts both in vitro and in vivo. Inhaled nitric oxide (NO) attenuates ECM accumulation, enhances lung growth, and decreases alveolar myofibroblast number in experimental models. We therefore hypothesized that NO attenuates TGF-β1-induced EMT in cultured AEC. Studies of the capacity for endogenous NO production in AEC revealed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) are expressed and active in AEC. Total NOS activity was 1.3 pmol·mg protein−1·min−1 with 67% derived from eNOS. TGF-β1 (50 pM) suppressed eNOS expression by more than 60% and activity by 83% but did not affect iNOS expression or activity. Inhibition of endogenous NOS with l-NAME led to spontaneous EMT, manifested by increased α-smooth muscle actin (α-SMA) expression and a fibroblast-like morphology. Provision of exogenous NO to TGF-β1-treated AEC decreased stress fiber-associated α-SMA expression and decreased collagen I expression by 80%. NO-treated AEC also retained an epithelial morphology and expressed increased lamellar protein, E-cadherin, and pro-surfactant protein B compared with those treated with TGF-β alone. These findings indicate that NO serves a critical role in preserving an epithelial phenotype and in attenuating EMT in AEC. NO-mediated regulation of AEC fate may have important implications in the pathophysiology and treatment of diseases such as IPF and BPD.

Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-β1

1998 ◽  
Vol 275 (1) ◽  
pp. F18-F24 ◽  
Author(s):  
Wei-Zhong Ying ◽  
Paul W. Sanders
Keyword(s):  
Nitric Oxide ◽  
Steady State ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Transforming Growth Factor ◽  
No Production ◽  
Dietary Salt ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Tgf Β1

Dietary salt controls production of nitric oxide (NO), a potent paracrine relaxation factor involved in glomerular filtration and salt excretion. We hypothesized that glomerular NO production was enhanced through endothelial nitric oxide synthase (NOS3). Rats in metabolic cages were studied after 4 days on 0.3% (Lo-salt) or 8.0% (Hi-salt) NaCl diet. Steady-state mRNA and protein levels of NOS3 and calcium-dependent NO production of isolated glomeruli from Hi-salt animals were greater than those values observed in glomeruli from Lo-salt rats. Because dietary salt enhanced glomerular production of transforming growth factor-β1 (TGF-β1) [W.-Z. Ying and P. W. Sanders. Am. J. Physiol. 274 ( Renal Physiol. 43): F635–F641, 1998], studies were then conducted to examine the interaction between NOS3 and TGF-β1. Glomerular steady-state levels of mRNA of NOS3 and TGF-β1 directly correlated ( r 2 = 0.946; P < 0.0001). A neutralizing antibody to TGF-β reduced NOS3 protein and NO production in cultured glomeruli from Hi-salt animals to levels seen in the Lo-salt glomeruli. Thus dietary salt increased glomerular expression of TGF-β1, which in turn augmented NO production through NOS3.

scholarly journals Nitric Oxide Synthase Gene Transfer Overcomes the Inhibition of Wound Healing by Sulfur Mustard in a Human Keratinocyte In Vitro Model

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroshi Ishida ◽  
Radharaman Ray ◽  
Jack Amnuaysirikul ◽  
Keiko Ishida ◽  
Prabhati Ray
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Nitric Oxide Synthase ◽  
Gene Transfer ◽  
Sulfur Mustard ◽  
No Production ◽  
Skin Injury ◽  
Inos Gene ◽  
Oxide Synthase

Sulfur mustard (SM) is a chemical warfare agent that causes extensive skin injury. Previously we reported that SM exposure resulted in suppression of inducible nitric oxide synthase (iNOS) expression to inhibit the healing of scratch wounds in a cultured normal human epidermal keratinocyte (NHEK) model. Based on this finding, the present study was to use adenovirus-mediated gene transfer of iNOS to restore the nitric oxide (NO) supply depleted by exposure to SM and to evaluate the effect of NO on wound healing inhibited by SM in NHEKs. The effect of the iNOS gene transfer on iNOS protein expression and NO generation were monitored by Western blot and flow cytometry, respectively. Wound healing with or without the iNOS gene transfer after SM exposure was assessed by light and confocal microscopy. The iNOS gene transfer via adenovirus resulted in overexpression of the iNOS and an increase in NO production regardless of SM exposure in the NHEK model. The gene transfer was also effective in overcoming the inhibition of wound healing due to SM exposure leading to the promotion of wound closure. The findings in this study suggest that the iNOS gene transfer is a promising therapeutic strategy for SM-induced skin injury.

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