Effects Of Rho Kinase Inhibition On Airway And Lung Tissue Inflammation, Extracellular Matrix Remodeling And Oxidative Stress Activation In Animals With Chronic Pulmonary Inflammation

Background. CrataBL is a protein isolated from Crataeva tapia bark. It has been shown to exhibit several biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. There are no studies evaluating the role of CrataBL in experimental asthma models. Aim. To evaluate the effects of CrataBL on lung mechanics, inflammation, remodeling, and oxidative stress activation of mice with allergic pulmonary inflammation. Materials and Methods. BALB/c mice (6-7 weeks old, 25-30g) were divided into four groups: nonsensitized and nontreated mice (C group, n=8); ovalbumin- (OVA-) sensitized and nontreated mice (OVA group, n=8); nonsensitized and CrataBL-treated mice (C+CR group, n=8); OVA-sensitized and CrataBL-treated mice (OVA+CR group, n=8). We evaluated hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), pulmonary inflammation, extracellular matrix remodeling, and oxidative stress markers. Results. CrataBL treatment in OVA-sensitized mice (OVA+CR group) attenuated the following variables compared to OVA-sensitized mice without treatment (OVA group) (all p<0.05): (1) respiratory system resistance (Rrs) and elastance (Ers) after methacholine challenge; (2) total cells, macrophages, polymorphonuclear cells, and lymphocytes in BALF; (3) eosinophils and volume fraction of collagen and elastic fibers in the airway and alveolar wall according to histopathological and morphometry analysis; (4) IL-4-, IL-5-, IL-13-, IL-17-, IFN-γ-, MMP-9-, TIMP-1-, TGF-β-, iNOS-, and NF-kB-positive cells and volume of 8-iso-PGF2α in airway and alveolar septa according to immunohistochemistry; and (5) IL-4, IL-5, and IFN-γ according to an ELISA. Conclusion. CrataBL contributes to the control of hyperresponsiveness, pulmonary inflammation, extracellular matrix remodeling, and oxidative stress responses in an animal model of chronic allergic pulmonary inflammation.

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Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00034.2012 ◽

2012 ◽

Vol 303 (11) ◽

pp. L939-L952 ◽

Cited By ~ 41

Author(s):

Samantha Souza Possa ◽

Homar Toledo Charafeddine ◽

Renato Fraga Righetti ◽

Patricia Angeli da Silva ◽

Rafael Almeida-Reis ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Airway Hyperresponsiveness ◽

Rho Kinase ◽

Extracellular Matrix Remodeling ◽

Repeated Treatment ◽

Matrix Remodeling ◽

Pathway Activation ◽

And Oxidative Stress ◽

Stress Activation

Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals′ pulmonary mechanics were evaluated, and exhaled nitric oxide (ENO) was collected. The lungs were removed, and histological analysis was performed using morphometry. Treatment with Y-27632 in sensitized animals reduced ENO concentrations, maximal responses of resistance, elastance of the respiratory system, eosinophil counts, collagen and elastic fiber contents, the numbers of cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-β, NF-κB, IFN-γ, and 8-iso-prostaglandin F2α contents compared with the untreated group ( P < 0.05). We observed positive correlations among the functional responses and inflammation, remodeling, and oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase pathway activation contributes to the potentiation of the hyperresponsiveness, inflammation, the extracellular matrix remodeling process, and oxidative stress activation. These results suggest that Rho-kinase inhibitors represent potential pharmacological tools for the control of asthma.

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Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy

Inflammation ◽

10.1007/s10753-018-0792-9 ◽

2018 ◽

Vol 41 (4) ◽

pp. 1460-1476 ◽

Cited By ~ 13

Author(s):

Passant E. Moustafa ◽

Noha F. Abdelkader ◽

Sally A. El Awdan ◽

Osama A. El-Shabrawy ◽

Hala F. Zaki

Keyword(s):

Oxidative Stress ◽

Extracellular Matrix ◽

Peripheral Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

And Oxidative Stress

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“Skin cancer, polyphenols, and oxidative stress” or Counteraction of oxidative stress, inflammation, signal transduction pathways, and extracellular matrix remodeling that mediate skin carcinogenesis by polyphenols

Cancer ◽

10.1016/b978-0-12-819547-5.00039-0 ◽

2021 ◽

pp. 439-450

Author(s):

Neena Philips ◽

Richard Richardson ◽

Halyna Siomyk ◽

David Bynum ◽

Salvador Gonzalez

Keyword(s):

Oxidative Stress ◽

Signal Transduction ◽

Extracellular Matrix ◽

Skin Cancer ◽

Skin Carcinogenesis ◽

Signal Transduction Pathways ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

And Oxidative Stress

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Abstract P137: Mir-122 is Associated With Stress-response Protein, Hemeoxygenase-1, for Regulation of Extracellular Matrix Remodeling in Renal Hypertension

Hypertension ◽

10.1161/hyp.68.suppl_1.p137 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Biswa P Das Purkayastha ◽

Lu Ren ◽

Sathnur Pushpakumar ◽

Utpal Sen

Keyword(s):

Oxidative Stress ◽

Extracellular Matrix ◽

Stress Response ◽

Mesangial Cells ◽

Renal Hypertension ◽

Regulation Of Gene Expression ◽

Micro Rna ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ang Ii

Oxidative stress is a major contributing factor in hypertension-induced kidney injury. Hemeoxygenase-1 (Ho-1) is stress response protein constitutively expressed by the proximal tubular epithelial cells in response to oxidative stress. MicroRNAs are single stranded RNA involved in the regulation of gene expression. MicroRNA-122 has been shown to regulate Ho-1 expression in hepatitis; however whether miR-122 regulates Ho-1 in hypertensive kidney is not known. The purpose of the study was to investigate the miRNA-122 Ho-1 regulation and determine its role in extracellular matrix remodeling in renal hypertension. In vitro experiments were done using mesangial cells, treated with/without 200 μM of Angiotensin-II (Ang-II). Ho-1 was induced by ~3.5 folds with Ang-II treatment. miR-122, Ho-1 regulator, was downregulated by >15 times in Ang-II treated cells. In vivo experiments were performed on WT (C57BL6/J) mice aged 12-14 wk and 75-78 wk. The animals were treated with Ang-II (1000ng/kg/min) for 4 weeks. Ho-1 is ~6 folds less in kidney of aged mice as compared to that in the young mice. Hypertension increases miR-122 expression to a greater extent (~5 folds) in aged animals. In Ho-1 knocked down mesangial cells, the extracellular matrix component, Collagen 1A1 (Col1a1), was increased by ~2 folds. In contrast, vascular endothelial growth factor ( Vegf ) and hypoxia-inducible factor ( Hif1 α ) were downregulated in Ho-1 depleted cells. In conclusion, micro RNA, miR-122, transcriptionally regulates Ho-1 as a repressor in kidney and thus affects Ho-1 mediated regulation of the extracellular remodeling in hypertension-induced renal damage.

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