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

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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Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal Cancer

The Journal of Urology ◽

10.1016/j.juro.2015.11.050 ◽

2016 ◽

Vol 195 (6) ◽

pp. 1892-1902 ◽

Cited By ~ 35

Author(s):

Joanna Boguslawska ◽

Hanna Kedzierska ◽

Piotr Poplawski ◽

Beata Rybicka ◽

Zbigniew Tanski ◽

...

Keyword(s):

Extracellular Matrix ◽

Renal Cancer ◽

Cellular Adhesion ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Poor Survival ◽

Expression Of Genes

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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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Hypoxia-increased expression of genes involved in inflammation, dedifferentiation, pro-fibrosis, and extracellular matrix remodeling of human bladder smooth muscle cells

In Vitro Cellular & Developmental Biology - Animal ◽

10.1007/s11626-016-0085-2 ◽

2016 ◽

Vol 53 (1) ◽

pp. 58-66 ◽

Cited By ~ 18

Author(s):

Bridget Wiafe ◽

Adetola Adesida ◽

Thomas Churchill ◽

Esther Ekpe Adewuyi ◽

Zack Li ◽

...

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Bladder Smooth Muscle ◽

Human Bladder ◽

Expression Of Genes

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Atrial endothelial cells senescence promotes thrombogenicity, inflammation and extracellular matrix remodeling: Role of the local Ang II/AT1 receptor pathway

Archives of Cardiovascular Diseases Supplements ◽

10.1016/j.acvdsp.2018.02.102 ◽

2018 ◽

Vol 10 (2) ◽

pp. 223 ◽

Cited By ~ 1

Author(s):

H. Hasan ◽

M. Abbas ◽

C. Auger ◽

E. Belcastro ◽

M.A. Farooq ◽

...

Keyword(s):

Extracellular Matrix ◽

Endothelial Cells ◽

At1 Receptor ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ang Ii

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Faculty Opinions recommendation of Sweet, yet underappreciated: Proteoglycans and extracellular matrix remodeling in heart disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732498270.793541733 ◽

2018 ◽

Author(s):

Nikos Karamanos

Keyword(s):

Extracellular Matrix ◽

Heart Disease ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽

10.3390/cells10051046 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1046

Author(s):

Jorge Martinez ◽

Patricio C. Smith

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Cell Metabolism ◽

Breast Tumors ◽

Extracellular Matrix Remodeling ◽

Type I ◽

Matrix Remodeling ◽

Desmoplastic Reaction ◽

The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

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