Limits...
Osteopontin is indispensible for AP1-mediated angiotensin II-related miR-21 transcription during cardiac fibrosis.

Lorenzen JM, Schauerte C, Hübner A, Kölling M, Martino F, Scherf K, Batkai S, Zimmer K, Foinquinos A, Kaucsar T, Fiedler J, Kumarswamy R, Bang C, Hartmann D, Gupta SK, Kielstein J, Jungmann A, Katus HA, Weidemann F, Müller OJ, Haller H, Thum T - Eur. Heart J. (2015)

Bottom Line: OPN and miR-21 were significantly increased in cardiac biopsies of patients with myocardial fibrosis.This was associated with enhanced cardiac collagen content, myofibroblast activation, ERK-MAP kinase as well as AKT signalling pathway activation and a reduced expression of Phosphatase and Tensin Homologue (PTEN) as well as SMAD7 in WT but not OPN KO mice.In vitro, Ang II induced expression of miR-21 in WT cardiac fibroblasts, while miR-21 levels were unchanged in OPN KO fibroblasts.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany Department of Internal Medicine, Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany lorenzen.johan@mh-hannover.de thum.thomas@mh-hannover.de.

No MeSH data available.


Related in: MedlinePlus

MiR-21 expression in mice following cardiotropic osteopontin-AAV9 injection (A) as well as osteopontin protein expression in hearts (B and C) compared with CTL-AAV9. Sirius red staining in paraffin-embedded sections of cardiac tissue of sham-operated mice (D), mice subjected to CTL-AAV9 and Ang II (E), osteopontin-AAV9 and Ang II (F), CTL-AAV9 and Ang II as well as locked-nucleic acid treatment targeting miR-21 (LNA-21, G), osteopontin-AAV9 and Ang II as well as LNA-21 (H), and quantification of results (I). n = 5 animals per group and analysis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4543785&req=5

EHV109F4: MiR-21 expression in mice following cardiotropic osteopontin-AAV9 injection (A) as well as osteopontin protein expression in hearts (B and C) compared with CTL-AAV9. Sirius red staining in paraffin-embedded sections of cardiac tissue of sham-operated mice (D), mice subjected to CTL-AAV9 and Ang II (E), osteopontin-AAV9 and Ang II (F), CTL-AAV9 and Ang II as well as locked-nucleic acid treatment targeting miR-21 (LNA-21, G), osteopontin-AAV9 and Ang II as well as LNA-21 (H), and quantification of results (I). n = 5 animals per group and analysis.

Mentions: In order to further identify the pro-fibrotic role of OPN in vivo, we generated cardiotropic OPN-AAV9 vectors for in vivo use (Figure 4). OPN-AAV9 alone increased both OPN and miR-21 expression (Figure 4A–C). OPN-AAV9 together with concomitant Ang II infusion significantly increased tissue fibrosis when compared with control CTL-AAV9-treated (with Ang II) and sham-operated animals (Figure 4D–F and I). Fibrosis development was highly attenuated by use of an LNA targeting miR-21 (LNA-21, Figure 4G–I). The reduction of fibrosis was more pronounced in CTL-AAV9-treated animals than in OPN-AAV9-treated animals.Figure 4


Osteopontin is indispensible for AP1-mediated angiotensin II-related miR-21 transcription during cardiac fibrosis.

Lorenzen JM, Schauerte C, Hübner A, Kölling M, Martino F, Scherf K, Batkai S, Zimmer K, Foinquinos A, Kaucsar T, Fiedler J, Kumarswamy R, Bang C, Hartmann D, Gupta SK, Kielstein J, Jungmann A, Katus HA, Weidemann F, Müller OJ, Haller H, Thum T - Eur. Heart J. (2015)

MiR-21 expression in mice following cardiotropic osteopontin-AAV9 injection (A) as well as osteopontin protein expression in hearts (B and C) compared with CTL-AAV9. Sirius red staining in paraffin-embedded sections of cardiac tissue of sham-operated mice (D), mice subjected to CTL-AAV9 and Ang II (E), osteopontin-AAV9 and Ang II (F), CTL-AAV9 and Ang II as well as locked-nucleic acid treatment targeting miR-21 (LNA-21, G), osteopontin-AAV9 and Ang II as well as LNA-21 (H), and quantification of results (I). n = 5 animals per group and analysis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543785&req=5

EHV109F4: MiR-21 expression in mice following cardiotropic osteopontin-AAV9 injection (A) as well as osteopontin protein expression in hearts (B and C) compared with CTL-AAV9. Sirius red staining in paraffin-embedded sections of cardiac tissue of sham-operated mice (D), mice subjected to CTL-AAV9 and Ang II (E), osteopontin-AAV9 and Ang II (F), CTL-AAV9 and Ang II as well as locked-nucleic acid treatment targeting miR-21 (LNA-21, G), osteopontin-AAV9 and Ang II as well as LNA-21 (H), and quantification of results (I). n = 5 animals per group and analysis.
Mentions: In order to further identify the pro-fibrotic role of OPN in vivo, we generated cardiotropic OPN-AAV9 vectors for in vivo use (Figure 4). OPN-AAV9 alone increased both OPN and miR-21 expression (Figure 4A–C). OPN-AAV9 together with concomitant Ang II infusion significantly increased tissue fibrosis when compared with control CTL-AAV9-treated (with Ang II) and sham-operated animals (Figure 4D–F and I). Fibrosis development was highly attenuated by use of an LNA targeting miR-21 (LNA-21, Figure 4G–I). The reduction of fibrosis was more pronounced in CTL-AAV9-treated animals than in OPN-AAV9-treated animals.Figure 4

Bottom Line: OPN and miR-21 were significantly increased in cardiac biopsies of patients with myocardial fibrosis.This was associated with enhanced cardiac collagen content, myofibroblast activation, ERK-MAP kinase as well as AKT signalling pathway activation and a reduced expression of Phosphatase and Tensin Homologue (PTEN) as well as SMAD7 in WT but not OPN KO mice.In vitro, Ang II induced expression of miR-21 in WT cardiac fibroblasts, while miR-21 levels were unchanged in OPN KO fibroblasts.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany Department of Internal Medicine, Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany lorenzen.johan@mh-hannover.de thum.thomas@mh-hannover.de.

No MeSH data available.


Related in: MedlinePlus