NDLI: MicroRNA-29, a key regulator of collagen expression in systemic sclerosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maurer, Britta Stanczyk, Joanna Jüngel, Astrid Akhmetshina, Alfiya Trenkmann, Michelle Brock, Matthias Kowal-Bielecka, Otylia Gay, Renate E. Michel, Beat A. Distler, Jörg H. W. Gay, Steffen Distler, Oliver
Description	Country affiliation: Switzerland Author Affiliation: Maurer B ( University Hospital Zurich and Zurich Center of Integrative Human Physiology, Zurich, Switzerland.)
Abstract	OBJECTIVE: To investigate the role of microRNA (miRNA) as posttranscriptional regulators of profibrotic genes in systemic sclerosis (SSc). METHODS: MicroRNA, which target collagens, were identified by in silico analysis. Expression of miRNA-29 (miR-29) was determined by TaqMan real-time polymerase chain reaction analysis of skin biopsy and fibroblast samples from SSc patients and healthy controls as well as in the mouse model of bleomycin-induced skin fibrosis. Cells were transfected with precursor miRNA (pre-miRNA)/anti-miRNA of miR-29 using Lipofectamine. Collagen gene expression was also studied in luciferase reporter gene assays. For stimulation, recombinant transforming growth factor beta (TGFbeta), platelet-derived growth factor B (PDGF-B), or interleukin-4 (IL-4) was used. The effects of inhibiting PDGF-B and TGFbeta signaling on the levels of miR-29 were studied in vitro and in the bleomycin model. RESULTS: We found that miR-29a was strongly down-regulated in SSc fibroblasts and skin sections as compared with the healthy controls. Overexpression in SSc fibroblasts significantly decreased, and accordingly, knockdown in normal fibroblasts increased, the levels of messenger RNA and protein for type I and type III collagen. In the reporter gene assay, cotransfection with pre-miR-29a significantly decreased the relative luciferase activity, which suggests a direct regulation of collagen by miR-29a. TGFbeta, PDGF-B, or IL-4 reduced the levels of miR-29a in normal fibroblasts to those seen in SSc fibroblasts. Similar to human SSc, the expression of miR-29a was reduced in the bleomycin model of skin fibrosis. Inhibition of PDGF-B and TGFbeta pathways by treatment with imatinib restored the levels of miR-29a in vitro and in the bleomycin model in vivo. CONCLUSION: These data add the posttranscriptional regulation of collagens by miR-29a as a novel aspect to the fibrogenesis of SSc and suggest miR-29a as a potential therapeutic target.
File Format	HTM / HTML
ISSN	00043591
e-ISSN	15290131
Journal	Arthritis & Rheumatism
Issue Number	6
Volume Number	62
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2010-06-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Micrornas Research Support, Non-u.s. Gov't Cells, Cultured Collagen Type I Metabolism Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Pathology Collagen Type Iii Scleroderma, Systemic Down-regulation Fibroblasts Genetics Skin Discipline Rheumatic Diseases
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Pharmacology (medical) Rheumatology

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