A role for bone morphogenetic proteins in the induction of cardiac myogenesis.

Schultheiss, Thomas M.; Burch, John; Lassar, Andrew B.

doi:10.1101/gad.11.4.451

Cited by 634 publications

(572 citation statements)

References 71 publications

(75 reference statements)

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“…However, to date, no small regulator targeting the myocardial fibrosis was reported. BMP-7 has been reported to be involved in cardiac myogenesis of chick embryo, and BMP signaling pathways are functional in cardiac myocytes from mice, rats, and humans (Schultheiss et al 1997;Wu et al 2014). To Relative mRNA expression levels of collagen3.…”

Section: Discussionmentioning

confidence: 99%

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Xiao

et al. 2018

Tohoku J. Exp. Med.

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Myocardial fibrosis after acute myocardial infarction (AMI) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation. Another 40 rats underwent LAD ligation were randomly grouped into saline-treated group (n = 20) and BMP-7-treated group (n = 20) which received saline treatment or exogenous BMP-7 treatment for 14 days, respectively. Two weeks after LAD ligation, the survival rate of BMP-7-treated AMI group was significantly improved compared to the saline group. Moreover, the cardiac function was preserved as shown by echocardiography examination, and the infarcted size was limited upon BMP-7 treatment. In addition, we investigated the role of TGF-β1 signaling pathway in BMP-7-mediated cardioprotective effects by analyzing the expression levels of TGF-β1, Smad 2 and Smad 3 in the infarct zone, border zone, and non-infarct zone. Western blot and quantitative PCR results suggested that BMP-7 attenuated myocardial fibrosis through counteracting TGF-β1 signaling pathway, thereby exerting cardioprotective effects. In conclusion, our data provide a potential therapeutic direction for preserving cardiac function and improving prognosis of AMI patients.

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Section: Discussionmentioning

confidence: 99%

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Xiao

et al. 2018

Tohoku J. Exp. Med.

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“…BMP2/4 are critical for cardiomyocyte induction and are expressed in anterior lateral plate endoderm and ventral mesoderm (Lyons et al, 1995;Schultheiss et al, 1997). BMP signaling appears to be interacting and coordinated with the canonical Wnt signaling wave, as it progresses anteroposteriorly across the bilateral heart fields.…”

Section: Dorsal Wnt Inhibitory Activity Is Coordinated With Ventral Bmentioning

confidence: 99%

Early temporal‐specific responses and differential sensitivity to lithium and Wnt‐3A exposure during heart development

Manisastry

Han

Linask

2006

Developmental Dynamics

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Members of both Wnt and bone morphogenetic protein (BMP) families of signaling molecules are important in heart development. We previously demonstrated that ␤-catenin, a key downstream intermediary of the canonical Wnt signaling pathway, delineates the dorsal boundary of the cardiac compartments in an anteroposterior progression. We hypothesized the progression involves canonical Wnt signaling and reflects development of the primary body axis of the embryo. A similar anteroposterior signaling wave leading to cardiac cell specification involves inductive signaling by BMP-2 synthesized by the underlying endoderm in anterior bilateral regions. Any molecule that disrupts the normal balance of Wnt and BMP concentrations within the heart field may be expected to affect early heart development. The canonical Wnt signaling step mimicked by lithium involves inactivation of glycogen synthase kinase-3␤ (GSK-3␤; Klein and Melton [1996] Proc. Natl. Acad. Sci. U. S. A. 93:8455-8459). We show that lithium, Wnt-3A, and an inhibitor of GSK-3␤, SB415286, affect early heart development at the cardiac specification stages. We demonstrate that normal expression patterns of key signaling molecules as Notch-1 and Dkk-1 are altered in the anterior mesoderm within the heart fields by a one-time exposure to lithium, or by noggin inhibition of BMP, at Hamburger and Hamilton (HH) stage 3 during chick embryonic development. The severity of developmental defects is greatest with exposure to lithium or Wnt-3A at HH stage 3 and decreases at HH stage 4. Taken together, our results demonstrate that there are temporal-specific responses and differential sensitivities to lithium/Wnt-3A exposure during early heart development.

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“…The cardiac-promoting activities of these molecules appear to correlate with their involvement in normal cardiogenesis in the embryo. In situ hybridization data in the developing chick, frog, and/or mouse has shown that BMP2, BMP4, FGF4, FGF8, WNT11, Dkk1, and crescent are expressed at the right time and place to act as primary stimulators of heart formation in the developing embryo (Kispert et al, 1996;Schultheiss et al, 1997;Shibata et al, 2000;Niehrs et al, 2001;Alsan and Schultheiss, 2002). Moreover, specific inhibition of the expression and/or activity of WNT11 or BMP can significantly diminish the formation of cardiac tissue in the vertebrate embryo (Schultheiss et al, 1997;Schlange et al, 2000;Pandur et al, 2002).…”

Section: Specification Of Precardiac Mesoderm Cellsmentioning

confidence: 99%

Stem cells and the formation of the myocardium in the vertebrate embryo

2003

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A major goal in cardiovascular biology is to repair diseased or damaged hearts with newly generated myocardial tissue. Stem cells offer a potential source of replacement myocytes for restoring cardiac function. Yet little is known about the nature of the cells that are able to generate myocardium and the conditions they require to form heart tissue. A source of information that may be pertinent to addressing these issues is the study of how the myocardium arises from progenitor cells in the early vertebrate embryo. Accordingly, this review will examine the initial events of cardiac developmental biology for insights into the identity and characteristics of the stem cells that can be used to generate myocardial tissue for therapeutic purposes. Anat Rec Part A 276A:2-12, 2004.

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A role for bone morphogenetic proteins in the induction of cardiac myogenesis.

Cited by 634 publications

References 71 publications

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Early temporal‐specific responses and differential sensitivity to lithium and Wnt‐3A exposure during heart development

Stem cells and the formation of the myocardium in the vertebrate embryo

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