Differential Expression of Oxidative Stress and Extracellular Matrix Remodeling Genes in Low- or High-Dose-Rate Photon-Irradiated Skin

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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Differential expression of extracellular matrix remodeling genes in rat model of hemorrhagic shock and resuscitation1,2

Journal of Surgical Research ◽

10.1016/j.jss.2004.08.025 ◽

2005 ◽

Vol 123 (2) ◽

pp. 235-244 ◽

Cited By ~ 7

Author(s):

Huazhen Chen ◽

Ryan Inocencio ◽

Hasan B. Alam ◽

Peter Rhee ◽

Elena Koustova

Keyword(s):

Extracellular Matrix ◽

Hemorrhagic Shock ◽

Differential Expression ◽

Rat Model ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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The Plant Proteinase Inhibitor CrataBL Plays a Role in Controlling Asthma Response in Mice

BioMed Research International ◽

10.1155/2018/9274817 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Anelize Sartori Santos Bortolozzo ◽

Adriana Palmeira Dias Rodrigues ◽

Fernanda Magalhães Arantes-Costa ◽

Beatriz Mangueira Saraiva-Romanholo ◽

Flávia Castro Ribas de Souza ◽

...

Keyword(s):

Oxidative Stress ◽

Extracellular Matrix ◽

Pulmonary Inflammation ◽

Lung Mechanics ◽

Elastic Fibers ◽

Extracellular Matrix Remodeling ◽

Alveolar Wall ◽

Polymorphonuclear Cells ◽

Matrix Remodeling ◽

And Oxidative Stress

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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