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

Hypertension ◽  
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.

Abstract P016: GYY4137, a Hydrogen Sulfide Donor, Mitigates Ang II-induced Extracellular Matrix Remodeling in Glomerular Endothelial and Mesangial Cells

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Matthew Amin ◽  
Sathnur Pushpakumar ◽  
Sourav Kundu ◽  
Geetansh Tyagi ◽  
Aaron Tyagi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Hydrogen Sulfide ◽  
Mesangial Cells ◽  
Collagen Iv ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Ang Ii ◽  
Hypertensive Nephropathy ◽  
Glomerular Endothelial Cells

Hypertensive nephropathy is associated with progressive alteration of extracellular matrix (ECM) components. Both mesangial and glomerular endothelial cells have the ability to synthesize and degrade ECM proteins such as collagens by changes in the activity of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Endo180 is an extracellular fibronectin type II domain involved in lysosomal degradation of collagen which has been shown to mitigate renal fibrosis. More recently, hydrogen sulfide (H2S) has also been shown to mitigate hypertensive renal remodeling, however, its mechanism remains unclear. In this study, our aim was to investigate whether Angiotensin-II (Ang II) treatment alters the expression of Endo180, MMPs and TIMPs leading to dysregulation of collagen metabolism and whether GYY4137 (H2S donor) restores their levels to achieve homeostasis. Mesangial and mouse glomerular endothelial cells (MCs and MGECs respectively) were treated without or with Ang II (200 nM) and GYY4137 (250 μM) for 48hrs. Cell lysates were analyzed for MMP-13, -14, TIMP-1, Endo180, and collagen IV by Western blot, RT-PCR, and immunohistochemistry. In MGECs, Ang II treatment compared to its control decreased MMP-13/TIMP-1 ratio (0.75±0.44 vs. 2.48 ±0.73), and upregulated MMP-14/TIMP-1 ratio (0.64±2.10 vs. 0.96±1.47), and collagen IV (0.77±0.07 vs. 0.58±0.06). GYY4137 treatment mitigated these changes. In contrast, Ang II treatment in MCs decreased Endo180 compared to control (0.72±0.04 vs. 1.07±0.23), but did not alter the expression of MMP-13/TIMP-1, MMP-14/TIMP-1 ratios, and collagen IV level compared to control or MGECs. Similarly, immunostaining showed downregulation of MMP-13 and Endo180 in Ang II treated MGECs which was normalized following GYY4137 treatment. Endo180 was also normalized in MCs following GYY4137 treatment however, there was no change in MMP-14/TIMP-1 ratio or collagen IV level. We conclude that Ang II treatment causes adverse ECM remodeling in MGECs via downregulation of Endo180 and MMP-13 and upregulation of MMP-14 and TIMP-1 and in MCs by decreasing Endo180, and GYY4137 mitigates these changes in part, by modulating Endo180/MMP/TIMP pathway.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
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.

scholarly journals Liraglutide ameliorated peripheral neuropathy in diabetic rats: Involvement of oxidative stress, inflammation and extracellular matrix remodeling

2018 ◽  
Vol 146 (2) ◽  
pp. 173-185 ◽  
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 Rats ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling

scholarly journals Angiotensin II-Treated Cardiac Myocytes Regulate M1 Macrophage Polarization via Transferring Exosomal PVT1

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Feng Cao ◽  
Zhe Li ◽  
Wenmao Ding ◽  
Ling Yan ◽  
Qingyan Zhao
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Myocyte ◽  
Macrophage Polarization ◽  
Life Quality ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Ang Ii ◽  
Expression Of Genes ◽  
M1 Polarization ◽  
M1 Macrophage

Atrial fibrillation (AF) seriously reduces the health and life quality of patients. It is necessary to explore the pathogenesis of AF and provide a new target for the treatment. Here, exosomes were identified using transmission electron microscopy and nanoparticle tracing analysis. Western blotting assay was performed to detect the expression of exosomal surface markers, extracellular matrix-related proteins, and IL-16. The expression of genes was measured using qRT-PCR. Flow cytometry was performed to examine the percentages of CD86- and CD163-positive macrophages. Besides, luciferase activity assay was performed to explore the combination between PVT1 and miR-145-5p and the combination between miR-145-5p and IL-16 3’UTR. The combination between PVT1 and miR-145-5p also was examined using RIP assay. In our study, we isolated human cardiac myocyte- (HCM-) derived exosomes successfully. Ang-II-treated HCM-derived exosomes (Ang-II-Exo) promoted M1 macrophage polarization. PVT1 was highly expressed in Ang-II-Exo. Ang-II-Exo induced macrophage to M1 polarization through transferring PVT1. Furthermore, our data showed that PVT1 increased the expression of IL-16 via sponging miR-145-5p. Finally, we proved that exosomal PVT1 could boost the extracellular matrix remodeling of atrial fibroblasts. Overall, our data demonstrated that Ang-II-Exo promoted the extracellular matrix remodeling of atrial fibroblasts via inducing M1 macrophage polarization by transferring PVT1. PVT1 facilitated M1 polarization macrophage via increasing IL-16 expression by sponging miR-145-5p. Our results provided a new evidence for PVT1 which might be a treatment target of AF.

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