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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

Ang II-induced inflammation and fibrosis: angiotensin II induces the mRNA expression of osteopontin (A), interleukin-6 (B), as well as macrophage chemoattractant protein-1 (C) in wild-type fibroblasts, while interleukin-6 (D) and macrophage chemoattractant protein-1 (E) levels remain unchanged in osteopontin knockout fibroblasts in response to angiotensin II. Angiotensin II induces the mRNA expression of osteopontin in vitro in cardiomyocytes (F) as well as the secretion of osteopontin in the cell-culture supernatant of cultured cardiomyocytes (G). n = 5 independent experiments. Expression of collagen I (H), osteopontin (I), as well as miR-21 (J) in cardiac biopsies of patients with myocardial fibrosis related to aortic stenosis (n = 15) compared with healthy control patients (n = 5). Concomitant angiotensin-receptor blocker treatment lowers elevated levels of osteopontin in biopsies of patients with myocardial fibrosis (K).
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EHV109F1: Ang II-induced inflammation and fibrosis: angiotensin II induces the mRNA expression of osteopontin (A), interleukin-6 (B), as well as macrophage chemoattractant protein-1 (C) in wild-type fibroblasts, while interleukin-6 (D) and macrophage chemoattractant protein-1 (E) levels remain unchanged in osteopontin knockout fibroblasts in response to angiotensin II. Angiotensin II induces the mRNA expression of osteopontin in vitro in cardiomyocytes (F) as well as the secretion of osteopontin in the cell-culture supernatant of cultured cardiomyocytes (G). n = 5 independent experiments. Expression of collagen I (H), osteopontin (I), as well as miR-21 (J) in cardiac biopsies of patients with myocardial fibrosis related to aortic stenosis (n = 15) compared with healthy control patients (n = 5). Concomitant angiotensin-receptor blocker treatment lowers elevated levels of osteopontin in biopsies of patients with myocardial fibrosis (K).

Mentions: First we treated cultured cardiac fibroblasts and cardiomyocytes with Ang II and found increased OPN mRNA (cardiac fibroblasts, Figure 1A; cardiomyocytes, Figure 1F) as well as enhanced secreted OPN in the supernatant (cardiomyocytes, Figure 1G). In line with this observation, myocardial tissue of patients with myocardial fibrosis related to aortic stenosis (n = 15) when compared with control patients (n = 5) showed increased levels of Collagen I and OPN (Figure 1H–I). Concomitant angiotensin receptor blocker (ARB) treatment in these patients lowered elevated levels of OPN (Figure 1K).Figure 1


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)

Ang II-induced inflammation and fibrosis: angiotensin II induces the mRNA expression of osteopontin (A), interleukin-6 (B), as well as macrophage chemoattractant protein-1 (C) in wild-type fibroblasts, while interleukin-6 (D) and macrophage chemoattractant protein-1 (E) levels remain unchanged in osteopontin knockout fibroblasts in response to angiotensin II. Angiotensin II induces the mRNA expression of osteopontin in vitro in cardiomyocytes (F) as well as the secretion of osteopontin in the cell-culture supernatant of cultured cardiomyocytes (G). n = 5 independent experiments. Expression of collagen I (H), osteopontin (I), as well as miR-21 (J) in cardiac biopsies of patients with myocardial fibrosis related to aortic stenosis (n = 15) compared with healthy control patients (n = 5). Concomitant angiotensin-receptor blocker treatment lowers elevated levels of osteopontin in biopsies of patients with myocardial fibrosis (K).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHV109F1: Ang II-induced inflammation and fibrosis: angiotensin II induces the mRNA expression of osteopontin (A), interleukin-6 (B), as well as macrophage chemoattractant protein-1 (C) in wild-type fibroblasts, while interleukin-6 (D) and macrophage chemoattractant protein-1 (E) levels remain unchanged in osteopontin knockout fibroblasts in response to angiotensin II. Angiotensin II induces the mRNA expression of osteopontin in vitro in cardiomyocytes (F) as well as the secretion of osteopontin in the cell-culture supernatant of cultured cardiomyocytes (G). n = 5 independent experiments. Expression of collagen I (H), osteopontin (I), as well as miR-21 (J) in cardiac biopsies of patients with myocardial fibrosis related to aortic stenosis (n = 15) compared with healthy control patients (n = 5). Concomitant angiotensin-receptor blocker treatment lowers elevated levels of osteopontin in biopsies of patients with myocardial fibrosis (K).
Mentions: First we treated cultured cardiac fibroblasts and cardiomyocytes with Ang II and found increased OPN mRNA (cardiac fibroblasts, Figure 1A; cardiomyocytes, Figure 1F) as well as enhanced secreted OPN in the supernatant (cardiomyocytes, Figure 1G). In line with this observation, myocardial tissue of patients with myocardial fibrosis related to aortic stenosis (n = 15) when compared with control patients (n = 5) showed increased levels of Collagen I and OPN (Figure 1H–I). Concomitant angiotensin receptor blocker (ARB) treatment in these patients lowered elevated levels of OPN (Figure 1K).Figure 1

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