Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
| Autor: | Mohamed seif el Islam Djelouat, Joyce Benchitrit, Ziad A. Massy, Eléonore M'Baya-Moutoula, Laurent Metzinger, Valérie Metzinger-Le Meuth, Ashraf Yusuf Rangrez, Lucie Hénaut |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Vascular smooth muscle
Anatomy and Physiology RHOB lcsh:Medicine Gene Expression Cardiovascular Muscle Smooth Vascular Mice RNA interference Molecular cell biology Versicans mir-223 Cell Movement lcsh:Science rhoB GTP-Binding Protein Musculoskeletal System Aorta Mice Knockout Multidisciplinary biology MEF2 Transcription Factors Cell migration Genomics Cell biology Extracellular Matrix Up-Regulation Nucleic acids Actin Cytoskeleton Myogenic Regulatory Factors cardiovascular system Versican Muscle Medicine Epigenetics Cellular Types Research Article medicine.medical_specialty Myocytes Smooth Muscle Primary Cell Culture Aortic Diseases Kruppel-Like Transcription Factors Down-Regulation MADS Domain Proteins Cardiovascular Pharmacology Phosphates Muscle Types Apolipoproteins E Downregulation and upregulation Vascular Biology Internal medicine medicine Genetics Animals Humans Vascular Calcification Biology Cell Proliferation Muscle Cells lcsh:R RNA stability medicine.disease Actin cytoskeleton Atherosclerosis MicroRNAs Endocrinology biology.protein RNA lcsh:Q Calcification |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 10, p e47807 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Backgound An elevated serum inorganic phosphate (Pi) level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs), with an emphasis on the role of microRNAs (miRNAs). Methodology/Principal Findings Exposure of human primary VSMCs in vitro to pathological levels of Pi increased calcification, migration rate and concomitantly reduced cell proliferation and the amount of the actin cytoskeleton. These changes were evidenced by significant downregulation of miRNA-143 (miR-143) and miR-145 and concomitant upregulation of their targets and key markers in synthetic VSMCs, such as Kruppel-like factors−4 and −5 and versican. Interestingly, we also found that miR-223 (a marker of muscle damage and a key factor in osteoclast differentiation) is expressed in VSMCs and is significantly upregulated in Pi-treated cells. Over-expressing miR-223 in VSMCs increased proliferation and markedly enhanced VSMC migration. Additionally, we found that the expression of two of the known miR-223 targets, Mef2c and RhoB, was highly reduced in Pi treated as well as miR-223 over-expressing VSMCs. To complement these in vitro findings, we also observed significant downregulation of miR-143 and miR-145 and upregulation of miR-223 in aorta samples collected from ApoE knock-out mice, which display vascular calcification. Conclusions/Significance Our results suggest that (i) high levels of Pi increase VSMC migration and calcification, (ii) altered expression levels of miR-223 could play a part in this process and (iii) miR-223 is a potential new biomarker of VSMC damage. |
| Databáze: | OpenAIRE |
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