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.Recombinant OPN directly activated miR-21, enhanced fibrosis, and activated the phosphoinositide 3-kinase pathway.OPN KO animals are protected from miR-21 increase and fibrosis development due to impaired AP-1 activation and fibroblast activation.

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 targets in osteopontin wild type and knockout mice: Protein expression as well as densitometric quantification of PTEN (A and B), SMAD7 (A and C), and PDCD4 (A and D) in wild type mice subjected to Ang II and locked-nucleic acid treatment targeting miR-21 (LNA-21) or control mismatch LNA (LNA–MM) treatment. Protein expression as well as densitometric quantification of PTEN (E and F), SMAD7 (E and G), and PDCD4 (E and H) in osteopontin knockout mice subjected to Ang II infusion. n = 6 animals per group and analysis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHV109F5: miR-21 targets in osteopontin wild type and knockout mice: Protein expression as well as densitometric quantification of PTEN (A and B), SMAD7 (A and C), and PDCD4 (A and D) in wild type mice subjected to Ang II and locked-nucleic acid treatment targeting miR-21 (LNA-21) or control mismatch LNA (LNA–MM) treatment. Protein expression as well as densitometric quantification of PTEN (E and F), SMAD7 (E and G), and PDCD4 (E and H) in osteopontin knockout mice subjected to Ang II infusion. n = 6 animals per group and analysis.

Mentions: We identified Phosphatase and tensin homolog (PTEN) and SMAD family member 7 (SMAD7) as targets of miR-21 in WT animals (Figure 5A–C) and WT cardiac fibroblasts (Supplementary material online, Figure S7A, C, and E). Programmed cell-death protein 4 (PDCD4) was tested as an additional target, but could not be confirmed in our study (Figure 5A and D for animals and Supplementary material online, Figure S7A and D for cells). MiR-21 silencing in vivo by LNA-21 treatment normalized the expression of PTEN and SMAD7 (Figure 5A–C). None of the aforementioned targets were regulated in OPN KO animals (Figure 5E–H) and OPN KO fibroblasts in vitro (Supplementary material online, Figure S7B and F–H), most likely related to unaltered levels of miR-21, further underlining the major regulatory role of OPN with regard to fibrosis development.Figure 5


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 targets in osteopontin wild type and knockout mice: Protein expression as well as densitometric quantification of PTEN (A and B), SMAD7 (A and C), and PDCD4 (A and D) in wild type mice subjected to Ang II and locked-nucleic acid treatment targeting miR-21 (LNA-21) or control mismatch LNA (LNA–MM) treatment. Protein expression as well as densitometric quantification of PTEN (E and F), SMAD7 (E and G), and PDCD4 (E and H) in osteopontin knockout mice subjected to Ang II infusion. n = 6 animals per group and analysis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHV109F5: miR-21 targets in osteopontin wild type and knockout mice: Protein expression as well as densitometric quantification of PTEN (A and B), SMAD7 (A and C), and PDCD4 (A and D) in wild type mice subjected to Ang II and locked-nucleic acid treatment targeting miR-21 (LNA-21) or control mismatch LNA (LNA–MM) treatment. Protein expression as well as densitometric quantification of PTEN (E and F), SMAD7 (E and G), and PDCD4 (E and H) in osteopontin knockout mice subjected to Ang II infusion. n = 6 animals per group and analysis.
Mentions: We identified Phosphatase and tensin homolog (PTEN) and SMAD family member 7 (SMAD7) as targets of miR-21 in WT animals (Figure 5A–C) and WT cardiac fibroblasts (Supplementary material online, Figure S7A, C, and E). Programmed cell-death protein 4 (PDCD4) was tested as an additional target, but could not be confirmed in our study (Figure 5A and D for animals and Supplementary material online, Figure S7A and D for cells). MiR-21 silencing in vivo by LNA-21 treatment normalized the expression of PTEN and SMAD7 (Figure 5A–C). None of the aforementioned targets were regulated in OPN KO animals (Figure 5E–H) and OPN KO fibroblasts in vitro (Supplementary material online, Figure S7B and F–H), most likely related to unaltered levels of miR-21, further underlining the major regulatory role of OPN with regard to fibrosis development.Figure 5

Bottom Line: OPN and miR-21 were significantly increased in cardiac biopsies of patients with myocardial fibrosis.Recombinant OPN directly activated miR-21, enhanced fibrosis, and activated the phosphoinositide 3-kinase pathway.OPN KO animals are protected from miR-21 increase and fibrosis development due to impaired AP-1 activation and fibroblast activation.

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