Association of Matrix metalloproteinase-3 with cardiogenic activity during Noggin-induced differentiation of mouse embryonic stem cells

Hong, Seonki; Kang, Jaeku; Park, Jung Jun; Ryu, Eun Sook; Choi, Sung Sik; Lee, Sang Ho; Lee, Jong Ho; Seo, Jeong Sun

doi:10.1016/j.ijcard.2008.11.156

Cited by 5 publications

(4 citation statements)

References 49 publications

(52 reference statements)

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“…showed that increased activity of MMP was required for spontaneous cardiomyocyte differentiation from mouse embryoid bodies embedded in 3D hydrogels, while treatment with the broad-spectrum MMP inhibitor PD166793 delayed the differentiation process35. Moreover, MMP-3 upregulation was found to be associated with Noggin-mediated cardiac lineage commitment of mouse ESCs, with MMP-3 knockdown leading to decreased expression of cardiac markers and cardiomyocyte yield36. Importantly, identifying and targeting the MMPs involved in the reprogramming process could enhance the efficiency and improve therapeutic outcomes of miRNA reprogramming in vivo and potentially lead to discovery of small reprogramming molecules that would obviate need for miRNA transfection.…”

Section: Discussionmentioning

confidence: 99%

Tissue-engineered 3-dimensional (3D) microenvironment enhances the direct reprogramming of fibroblasts into cardiomyocytes by microRNAs

Dal‐Pra

Mirotsou

et al. 2016

Sci Rep

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We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. Reprogramming of cardiac fibroblasts by miR combo in vivo is associated with improved cardiac function following myocardial infarction. However, the efficiency of direct reprogramming in vitro is relatively modest and new strategies beyond the traditional two-dimensional (2D) culture should be identified to improve reprogramming process. Here, we report that a tissue-engineered three-dimensional (3D) hydrogel environment enhanced miR combo reprogramming of neonatal cardiac and tail-tip fibroblasts. This was associated with significantly increased MMPs expression in 3D vs. 2D cultured cells, while pharmacological inhibition of MMPs blocked the effect of the 3D culture on enhanced miR combo mediated reprogramming. We conclude that 3D tissue-engineered environment can enhance the direct reprogramming of fibroblasts to cardiomyocytes via a MMP-dependent mechanism.

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Section: Discussionmentioning

confidence: 99%

Tissue-engineered 3-dimensional (3D) microenvironment enhances the direct reprogramming of fibroblasts into cardiomyocytes by microRNAs

Dal‐Pra

Mirotsou

et al. 2016

Sci Rep

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“…For example, matrix remodeling by metalloproteinases (MMP) can support self-renewal of ESC, presumably by mobilizing pluripotency factors sequestered in the surrounding cell matrix (Przybyla et al 2013). Another example is the potentiating role of MMP-3 in cardiac muscle differentiation in ESC embryoid bodies (Hong et al 2010). Finally, it is interesting to note the recent report highlighting a connection between the activation of innate cellular inflammatory processes and its enhancement of nuclear reprogramming (Lee et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Proteome array identification of bioactive soluble proteins/peptides in Matrigel: relevance to stem cell responses

Talbot

Caperna

2014

Cytotechnology

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Matrigel and similar commercial products are extracts of the Engelbreth-Holm-Swarm sarcoma that provide a basement-membrane-like attachment substrate or gel that is used to grow cells on or in, respectively. To ascertain further what proteins may be present in Matrigel, besides its major basement-membrane constituents, an analysis of the expressed liquid of gelled Matrigel was performed using proteome array technology. Among the growth factors/cytokines assayed, high positive detection was found for IGFBP1, IGFBP3, LIF, platelet factor 4, PlGF-2, and VEGF; moderate reactivity was found for cyr61, IGFBP2, IGFBP6, IL-1ra, and NOV; and low, but detectable, responses occurred for aFGF, IL-13, IL-23, M-CSF, and VEGF-B. Among the chemokines assayed, high positive detection was found for MIG and serpin E1; moderate reactivity was found for IP-10, MCP-1, and MCP-5, and low, but detectable, responses occurred for CXCL16, I-TAC, and MIP-1α. Among the other biologically active proteins assayed, high positive detection was found for adiponectin, C5a, endocan, lipocalin-2, sICAM-1, MMP-3, and TIMP-1; moderate reactivity was found for C-reactive protein, coagulation factor III, endoglin, endostatin/collagen XVIII, endothelin-1, ICAM-1, MMP-9, osteopontin, pentraxin-3, and RANTES; and low, but detectable, responses occurred for fetuin A, MMP-8, pentraxin-2, RBP4, resistin, and TIMP-4. The study found several growth factors, chemokines, and biologically active proteins not previously identified in Matrigel, and this may have significance to the interpretations of observed cellular responses when cells are grown on or in Matrigel.

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“…Many of the genes we identified as being regulated by HOXB4 were also identified in other microarray analysis of differentiation conditions designed to promote paraxial mesoderm formation [38] [39]. For example, Frzb , Lhx1 , Evx‐1 , Eomes , Mesp1 , Cdh11 , Gsc , and Cyp26a1 were identified in the PDGFRα + subpopulation of paraxial mesoderm [38], and Tbx6 , Evx1 , Mesp1 , Agtrl1 , Sox9 , and Dll3 were upregulated on addition of the BMP4 inhibitor Noggin to ESCs [39]. Noggin and Follistatin promote the formation of paraxial mesoderm by blocking BMP signaling [40], and we observed that the expression of both of these inhibitors was induced by HOXB4.…”

Section: Discussionmentioning

confidence: 99%

HOXB4 Can Enhance the Differentiation of Embryonic Stem Cells by Modulating the Hematopoietic Niche

et al. 2012

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Hematopoietic differentiation of embryonic stem cells (ESCs) in vitro has been used as a model to study early hematopoietic development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells (HPCs) where it promotes self-renewal, but it is also expressed in the primitive streak of the gastrulating embryo. This led us to hypothesize that HOXB4 might modulate gene expression in prehematopoietic mesoderm and that this property might contribute to its prohematopoietic effect in differentiating ESCs. To test our hypothesis, we developed a conditionally activated HOXB4 expression system using the mutant estrogen receptor (ER T2 ) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ESCs led to an increase in hematopoietic differentiation. Expression profiling revealed an increase in the expression of genes associated with paraxial mesoderm that gives rise to the hematopoietic niche. Therefore, we considered that HOXB4 might modulate the formation of the hematopoietic niche as well as the production of hematopoietic cells per se. Cell mixing experiments supported this hypothesis demonstrating that HOXB4 activation can generate a paracrine as well as a cell autonomous effect on hematopoietic differentiation. We provide evidence to demonstrate that this activity is partly mediated by the secreted protein FRZB. STEM CELLS 2012;30:150-160 Disclosure of potential conflicts of interest is found at the end of this article.

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Association of Matrix metalloproteinase-3 with cardiogenic activity during Noggin-induced differentiation of mouse embryonic stem cells

Cited by 5 publications

References 49 publications

Tissue-engineered 3-dimensional (3D) microenvironment enhances the direct reprogramming of fibroblasts into cardiomyocytes by microRNAs

Tissue-engineered 3-dimensional (3D) microenvironment enhances the direct reprogramming of fibroblasts into cardiomyocytes by microRNAs

Proteome array identification of bioactive soluble proteins/peptides in Matrigel: relevance to stem cell responses

HOXB4 Can Enhance the Differentiation of Embryonic Stem Cells by Modulating the Hematopoietic Niche

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