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Cited by 21TGF-β signaling in diseasesCancer Cells and MetastasisKruppel-like factors research

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The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition

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Sobierajska, Katarzyna, Ciszewski, Wojciech M., Macierzynska-Piotrowska, Ewa, Klopocka, Wanda, Przygodzka, Patrycja, Karakula, Magdalena, Pestka, Karolina, Wawro, Marta E., Niewiarowska, Jolanta·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21165875PMC PMC7461591
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Abstract

Endothelial–mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human snail promoter regulation in TGF-β-stimulated human endothelial cells. Although in silico analysis revealed that the snail promoter’s regulatory fragment contains one GCCG and two SP1 motifs that could be occupied by MRTFs, the genetic study confirmed that MRTF binds only to SP1 sites to promote snail expression. The more accurate studies revealed that MRTF-A binds to both SP1 elements, whereas MRTF-B to only one (SP1near). Although we found that each MRTF alone is capable of inducing snail expression, the direct cooperation of these proteins is required to reinforce snail expression and promote the late stages of EndMT within 48 hours. Furthermore, genetic and biochemical analysis revealed that MRTF-B alone could induce the late stage of EndMT. However, it requires a prolonged time. Therefore, we concluded that MRTFs might cause EndMT in a fast- and slow-dependent manner. Based on MRTF-dependent Snail upregulation, we recognized that TGF-β1, as an MRTF-B regulator, is involved in slow EndMT induction, whereas TGF-β2, which altered both MRTF-A and MRTF-B expression, promotes a fast EndMT process.

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Figure 1 Characteristics of the TGF-β2-induced endothelial–mesenchymal transition (EndMT) in HUVEC. Cells were incubated with TGF-β2 (10 ng/mL) for 48 h or alone. Subsequently, (A) the level of EndMT markers was evaluated using Western blot assay with the appropriate antibodies. The background was subtracted and the area for each protein peak was determined. Protein levels were normalized to GAPDH. (B) Cell morphology was observed under the microscope. Representative images are shown and a quantitative analysis of the mean of elongation ratio from three independent experiments was performed in Meta®Morph. Bars, 30 μm. (C) Contraction markers were determined by Western blot analysis. The relative protein level was quantified using scan densitometry. The background was subtracted and the area for each protein peak was determined. Protein levels were normalized to GAPDH. Subsequently, (D) the adhesion properties to collagen I was analyzed. Cells were placed on a collagen I pre-coated well for 1 h to adhere. After washing, the cells were stained, and the total cell-associated protein was determined using a microplate reader at 595 nm. The results are presented as the means ± SD (N = 3); * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0005.
Figure 1 Characteristics of the TGF-β2-induced endothelial–mesenchymal transition (EndMT) in HUVEC. Cells were incubated with TGF-β2 (10 ng/mL) for 48 h or alone. Subsequently, (A) the level of EndMT markers was evaluated using Western blot assay with the appropriate antibodies. The background was subtracted and the area for each protein peak was determined. Protein levels were normalized to GAPDH. (B) Cell morphology was observed under the microscope. Representative images are shown and a quantitative analysis of the mean of elongation ratio from three independent experiments was performed in Meta®Morph. Bars, 30 μm. (C) Contraction markers were determined by Western blot analysis. The relative protein level was quantified using scan densitometry. The background was subtracted and the area for each protein peak was determined. Protein levels were normalized to GAPDH. Subsequently, (D) the adhesion properties to collagen I was analyzed. Cells were placed on a collagen I pre-coated well for 1 h to adhere. After washing, the cells were stained, and the total cell-associated protein was determined using a microplate reader at 595 nm. The results are presented as the means ± SD (N = 3); * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0005.CC BY · PubMed Central
Figure 2 TGF-β2-induced myocardin-related transcription factor (MRTF) upregulation affected their nucleus accumulation. HMEC-1 cells and HUVECs were incubated with TGF-β2 (10 ng/mL) for 24, 36, 48, 60, and 72 h, or alone. Subsequently, (A) expression of MRTF-A and MRTF-B was analyzed by real-time PCR. The protein levels of the MRTFs were determined by Western blot analysis in (B) total lysate and (C) the nucleus and cytoplasm fraction of the analyzed cells. The background was subtracted and the area for each protein peak was determined. In the analysis of the MRTFs, the translocation MRTF-A or -B level was determined as a % of the total MRTF-A or –B. Protein levels were normalized to GAPDH (total lysate or cytoplasm fraction) or His3 (nuclear fraction). Blots are representative of three independent experiments. (D) The localization of MRTF-A and MRTF-B in the cellular compartments were analyzed using a confocal microscope. MRTFs were stained with antibodies conjugated with FITC. The white bar represents a 30 μm length. Representative images are shown. The results are presented as the means ± SD (N ≥ 3); ** p < 0.01, *** p < 0.001.
Figure 2 TGF-β2-induced myocardin-related transcription factor (MRTF) upregulation affected their nucleus accumulation. HMEC-1 cells and HUVECs were incubated with TGF-β2 (10 ng/mL) for 24, 36, 48, 60, and 72 h, or alone. Subsequently, (A) expression of MRTF-A and MRTF-B was analyzed by real-time PCR. The protein levels of the MRTFs were determined by Western blot analysis in (B) total lysate and (C) the nucleus and cytoplasm fraction of the analyzed cells. The background was subtracted and the area for each protein peak was determined. In the analysis of the MRTFs, the translocation MRTF-A or -B level was determined as a % of the total MRTF-A or –B. Protein levels were normalized to GAPDH (total lysate or cytoplasm fraction) or His3 (nuclear fraction). Blots are representative of three independent experiments. (D) The localization of MRTF-A and MRTF-B in the cellular compartments were analyzed using a confocal microscope. MRTFs were stained with antibodies conjugated with FITC. The white bar represents a 30 μm length. Representative images are shown. The results are presented as the means ± SD (N ≥ 3); ** p < 0.01, *** p < 0.001.CC BY · PubMed Central
Figure 3 Regulation of the MRTFs caused modulation of snail expression. (A) Effect of MRTF-A or MRTF-B downregulation using siRNA treatment on the Snail level in TGF-β2-induced cells was analyzed by a Western blot assay. Subsequently, (B) MRTF-A (Clone 1—cl1A; Clone 4—cl4A) or MRTF-B (Clone 2—cl2B; Clone 6—cl6B) stably transfected HMEC-1 cells and MRTF-A (mA) or MRTF-B (mB) transiently transfected HUVECs were analyzed. Additionally, the control of the cell transfection clones with only an empty vector (pcDNA) was tested. (C) Next, a similar analysis of the Snail level was done. The protein level in each sample was determined using scan densitometry in compared to GAPDH (as the normalization). Blots are representative of three independent experiments. The results are presented as the means ± SD (N ≥ 3); * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 3 Regulation of the MRTFs caused modulation of snail expression. (A) Effect of MRTF-A or MRTF-B downregulation using siRNA treatment on the Snail level in TGF-β2-induced cells was analyzed by a Western blot assay. Subsequently, (B) MRTF-A (Clone 1—cl1A; Clone 4—cl4A) or MRTF-B (Clone 2—cl2B; Clone 6—cl6B) stably transfected HMEC-1 cells and MRTF-A (mA) or MRTF-B (mB) transiently transfected HUVECs were analyzed. Additionally, the control of the cell transfection clones with only an empty vector (pcDNA) was tested. (C) Next, a similar analysis of the Snail level was done. The protein level in each sample was determined using scan densitometry in compared to GAPDH (as the normalization). Blots are representative of three independent experiments. The results are presented as the means ± SD (N ≥ 3); * p < 0.05, ** p < 0.01, *** p < 0.001.CC BY · PubMed Central
Figure 4 MRTF overexpression resulted in their activation, nuclear accumulation, and induction contraction and adhesion ability. (A) MRTF-A and MRTF-B localization were analyzed by Western blotting of the cytosol and nucleus fractions isolated from transfected cells. (B) The localization of MRTF-A and MRTF-B in the cellular compartments were analyzed using a confocal microscope. MRTFs were stained with antibodies conjugated with FITC. The white bar represents a 30 μm length. Representative images are shown. (C) Additionally, an IP assay of the cytosol fraction protein was applied. The MRTFs that interacted with the actin was precipitated with mouse anti-actin protein and subsequently analyzed by a Western blot assay with anti-rabbit MRTF-A or MRTF-B antibodies. (D) Contraction markers, such as α-SMA, caldesmon, and tropomyosin, were determined by Western blot analysis. For (A–D), the protein level in each sample was determined using scan densitometry. The results were normalized to GAPDH (cytosol and a nuclear fraction or total lysates) or Histone3 (His3, cytosol and nucleus fraction), or total the MRTFs (IP assay). Blots are representative of three independent experiments. The results are presented as the means ± SD (N = 3); * p < 0.05, ** p < 0.01, *** p < 0.001. (E) Changing in the cell morphology was observed under the microscope. Representative images are shown in the supplementary data (Figure S5) and a quantitative analysis of mean of the elongation ratio ((N = 3); ** p < 0.01, *** p < 0.001) was performed in Meta®Morph. Bars, 30 μm. (F) Subsequently, adhesion properties to collagen I was analyzed. Cells were placed on the collagen I pre-coated well for 1 h to adhere. After washing, the cells were stained, and the total cell-associated protein was determined using a microplate reader at 595 nm. The results are presented as the means ± SD (N = 5); ** p < 0.01, *** p < 0.001. (G) The effect of MRTF-A- or MRTF-B-overexpression on cell movement by the wound healing assay was studied. An appropriate cell number was seeded on 12-well plates pre-coated with collagen 1 (Coll). A total of 48 h later (after 4 h starvation in an FBS-free medium), a monolayer of confluent cells was wounded and images thereof were captured at the following times: 0, 2, 4, 6, 8, 10, 12, and 24 h. The results are given as the standard error of the mean of the cell front velocity ± SD (N = 4); *** p < 0.001.
Figure 4 MRTF overexpression resulted in their activation, nuclear accumulation, and induction contraction and adhesion ability. (A) MRTF-A and MRTF-B localization were analyzed by Western blotting of the cytosol and nucleus fractions isolated from transfected cells. (B) The localization of MRTF-A and MRTF-B in the cellular compartments were analyzed using a confocal microscope. MRTFs were stained with antibodies conjugated with FITC. The white bar represents a 30 μm length. Representative images are shown. (C) Additionally, an IP assay of the cytosol fraction protein was applied. The MRTFs that interacted with the actin was precipitated with mouse anti-actin protein and subsequently analyzed by a Western blot assay with anti-rabbit MRTF-A or MRTF-B antibodies. (D) Contraction markers, such as α-SMA, caldesmon, and tropomyosin, were determined by Western blot analysis. For (A–D), the protein level in each sample was determined using scan densitometry. The results were normalized to GAPDH (cytosol and a nuclear fraction or total lysates) or Histone3 (His3, cytosol and nucleus fraction), or total the MRTFs (IP assay). Blots are representative of three independent experiments. The results are presented as the means ± SD (N = 3); * p < 0.05, ** p < 0.01, *** p < 0.001. (E) Changing in the cell morphology was observed under the microscope. Representative images are shown in the supplementary data (Figure S5) and a quantitative analysis of mean of the elongation ratio ((N = 3); ** p < 0.01, *** p < 0.001) was performed in Meta®Morph. Bars, 30 μm. (F) Subsequently, adhesion properties to collagen I was analyzed. Cells were placed on the collagen I pre-coated well for 1 h to adhere. After washing, the cells were stained, and the total cell-associated protein was determined using a microplate reader at 595 nm. The results are presented as the means ± SD (N = 5); ** p < 0.01, *** p < 0.001. (G) The effect of MRTF-A- or MRTF-B-overexpression on cell movement by the wound healing assay was studied. An appropriate cell number was seeded on 12-well plates pre-coated with collagen 1 (Coll). A total of 48 h later (after 4 h starvation in an FBS-free medium), a monolayer of confluent cells was wounded and images thereof were captured at the following times: 0, 2, 4, 6, 8, 10, 12, and 24 h. The results are given as the standard error of the mean of the cell front velocity ± SD (N = 4); *** p < 0.001.CC BY · PubMed Central
Figure 5 Binding of the MRTFs to the −612/−431 sequence of the human snail promoter. (A) Schematic map of the snail promoter with potential activation sites for the MRTFs. (B) Nuclear extracts prepared from the HMEC-1 cells or HUVECs were used for the EMSA assay. For competition experiments, unlabeled competitor oligonucleotides in 200-fold molar excess were used. For the supershift experiments, the rabbit monoclonal anti-MRTF-A or anti-MRTF-B antibodies were used. (C) Snail luciferase constructs were studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-overexpressed HMEC-1 cells or HUVECs. The following constructs were used: −997/90, −612/90, −492/90, −431/90, and −294/90. Results are given as the standard error of the mean of the relative luciferase activity (N = 3).
Figure 5 Binding of the MRTFs to the −612/−431 sequence of the human snail promoter. (A) Schematic map of the snail promoter with potential activation sites for the MRTFs. (B) Nuclear extracts prepared from the HMEC-1 cells or HUVECs were used for the EMSA assay. For competition experiments, unlabeled competitor oligonucleotides in 200-fold molar excess were used. For the supershift experiments, the rabbit monoclonal anti-MRTF-A or anti-MRTF-B antibodies were used. (C) Snail luciferase constructs were studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-overexpressed HMEC-1 cells or HUVECs. The following constructs were used: −997/90, −612/90, −492/90, −431/90, and −294/90. Results are given as the standard error of the mean of the relative luciferase activity (N = 3).CC BY · PubMed Central
Figure 6 Role of the SP1 motifs in MRTFs-dependent snail expression regulation. (A) Sequences of mutated GCCG- and SP1-binding sites. Comparison of SP1 sequence localization in the mammalian snail promoter (B). Snail luciferase mutated constructs were studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-overexpressed HMEC-1 cells or HUVECs. The constructs with mutGCCG, mutSP1far, and mutSP1near were mutated as indicated in the figure. The results are given as the standard error of the mean of the relative luciferase activity (N = 3). (C) Nuclear extracts prepared from the HMEC-1 cells were used for the EMSA assay. For competition experiments, unlabeled competitor oligonucleotides, wild-type, or mutated (mutGCCG, mutSP1far, mutSP1near) oligonucleotides were added. For the supershift experiments, the rabbit monoclonal anti-MRTF-A or anti-MRTF-B antibodies and isotype control were used. (D) The chip assay was performed in HMEC-1 cells. Chromatin was fragmented and immunoprecipitated with normal rabbit IgG, anti-MRTF-A, and anti-MRTF-B antibodies. Immunoprecipitated DNA was amplified by PCR and separated on an agarose gel and visualized. The representative inverted gel images are shown. The results are presented as the means ± SD (N = 3).
Figure 6 Role of the SP1 motifs in MRTFs-dependent snail expression regulation. (A) Sequences of mutated GCCG- and SP1-binding sites. Comparison of SP1 sequence localization in the mammalian snail promoter (B). Snail luciferase mutated constructs were studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-overexpressed HMEC-1 cells or HUVECs. The constructs with mutGCCG, mutSP1far, and mutSP1near were mutated as indicated in the figure. The results are given as the standard error of the mean of the relative luciferase activity (N = 3). (C) Nuclear extracts prepared from the HMEC-1 cells were used for the EMSA assay. For competition experiments, unlabeled competitor oligonucleotides, wild-type, or mutated (mutGCCG, mutSP1far, mutSP1near) oligonucleotides were added. For the supershift experiments, the rabbit monoclonal anti-MRTF-A or anti-MRTF-B antibodies and isotype control were used. (D) The chip assay was performed in HMEC-1 cells. Chromatin was fragmented and immunoprecipitated with normal rabbit IgG, anti-MRTF-A, and anti-MRTF-B antibodies. Immunoprecipitated DNA was amplified by PCR and separated on an agarose gel and visualized. The representative inverted gel images are shown. The results are presented as the means ± SD (N = 3).CC BY · PubMed Central
Figure 7 Direct MRTF-A and MRTF-B cooperation is required for complete regulation of snail expression in TGF-β2-induced EndMT. HMEC-1 cells and HUVECs were incubated with TGF-β2 (10 ng/mL) for 48 h. As the control, non-stimulated cells were used. Subsequently, (A) Snail luciferase constructs were studied in MRTF-A-, MRTF-B-, or both MRTFs silenced (MRTF-A–MRTF-B-silenced) HMEC-1 cells or HUVECs. The following constructs were used: −997/90, −612/90, and −492/90. (B) Snail luciferase constructs with mutations in CGGC or SP1 fragments were analyzed in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-silenced HMEC-1 cells or HUVECs. The constructs with mutGCCG, mutSP1far, and mutSP1near were made as indicated previously. (C) HMEC-1 cells were incubated with TGF-β2 or TGF-β1 (10 ng/mL) for 24, 48, 60, and 72 h. As the control, non-induced cells were applied. Subsequently, the Snail luciferase construct (-997/90) was studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-silenced HMEC-1 cells. For (A) and (B), results are given as the standard error of the mean of the relative luciferase activity (N = 3). Then, a chip assay was performed in the HMEC-1 cells incubated with TGF-β2 (10 ng/mL) for 48 (C) or 72 h (D). Chromatin was fragmented and immunoprecipitated with normal rabbit IgG, anti-MRTF-A, and anti-MRTF-B antibodies. For the Re-Chip assay, immunoprecipitated DNA was diluted 10 times and re-immunoprecipitated with normal rabbit IgG, anti-MRTF-A, and anti-MRTF-B antibodies. Immunoprecipitated and re-immunoprecipitated DNA was amplified by PCR and separated on an agarose gel and visualized. Representative inverted gel images are shown. The results are presented as the means ± SD (N = 3).
Figure 7 Direct MRTF-A and MRTF-B cooperation is required for complete regulation of snail expression in TGF-β2-induced EndMT. HMEC-1 cells and HUVECs were incubated with TGF-β2 (10 ng/mL) for 48 h. As the control, non-stimulated cells were used. Subsequently, (A) Snail luciferase constructs were studied in MRTF-A-, MRTF-B-, or both MRTFs silenced (MRTF-A–MRTF-B-silenced) HMEC-1 cells or HUVECs. The following constructs were used: −997/90, −612/90, and −492/90. (B) Snail luciferase constructs with mutations in CGGC or SP1 fragments were analyzed in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-silenced HMEC-1 cells or HUVECs. The constructs with mutGCCG, mutSP1far, and mutSP1near were made as indicated previously. (C) HMEC-1 cells were incubated with TGF-β2 or TGF-β1 (10 ng/mL) for 24, 48, 60, and 72 h. As the control, non-induced cells were applied. Subsequently, the Snail luciferase construct (-997/90) was studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-silenced HMEC-1 cells. For (A) and (B), results are given as the standard error of the mean of the relative luciferase activity (N = 3). Then, a chip assay was performed in the HMEC-1 cells incubated with TGF-β2 (10 ng/mL) for 48 (C) or 72 h (D). Chromatin was fragmented and immunoprecipitated with normal rabbit IgG, anti-MRTF-A, and anti-MRTF-B antibodies. For the Re-Chip assay, immunoprecipitated DNA was diluted 10 times and re-immunoprecipitated with normal rabbit IgG, anti-MRTF-A, and anti-MRTF-B antibodies. Immunoprecipitated and re-immunoprecipitated DNA was amplified by PCR and separated on an agarose gel and visualized. Representative inverted gel images are shown. The results are presented as the means ± SD (N = 3).CC BY · PubMed Central
Figure 8 TGF-β1 induced slow EndMT in HMEC-1 cells. (A) HMEC-1 cells were incubated with TGF-β2 or TGF-β1 (10 ng/mL) for 24, 48, 60, or 72 h, or alone. Subsequently, the Snail luciferase construct (-997/90) was studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-silenced HMEC-1 cells. Results are given as the standard error of the mean of the relative luciferase activity (N = 3). (B) Cells were incubated with TGF-β1 (10 ng/mL) for the indicated time points. Then, the expressions of the MRTFs were analyzed by real-time PCR and the protein level was determined by a Western blot analysis of the total lysate. Cells were incubated with TGF-β1 (10 ng/mL) for 48, 72 h, or alone. Subsequently, (C) the level of Snail and (D) the levels of EndMT markers were evaluated using Western blot assays with the appropriate antibodies. For the protein level analysis, the background was subtracted and the area for each protein peak was determined. Protein levels were normalized to GAPDH. (E) Cell morphology was observed under the microscope. Representative images are shown and quantitative analysis of the mean of elongation ratio from three independent experiments was performed in Meta®Morph. Bars, 30 μm. The results are presented as the means ± SD (N = 3); *** p < 0.001.
Figure 8 TGF-β1 induced slow EndMT in HMEC-1 cells. (A) HMEC-1 cells were incubated with TGF-β2 or TGF-β1 (10 ng/mL) for 24, 48, 60, or 72 h, or alone. Subsequently, the Snail luciferase construct (-997/90) was studied in MRTF-A-, MRTF-B-, or MRTF-A–MRTF-B-silenced HMEC-1 cells. Results are given as the standard error of the mean of the relative luciferase activity (N = 3). (B) Cells were incubated with TGF-β1 (10 ng/mL) for the indicated time points. Then, the expressions of the MRTFs were analyzed by real-time PCR and the protein level was determined by a Western blot analysis of the total lysate. Cells were incubated with TGF-β1 (10 ng/mL) for 48, 72 h, or alone. Subsequently, (C) the level of Snail and (D) the levels of EndMT markers were evaluated using Western blot assays with the appropriate antibodies. For the protein level analysis, the background was subtracted and the area for each protein peak was determined. Protein levels were normalized to GAPDH. (E) Cell morphology was observed under the microscope. Representative images are shown and quantitative analysis of the mean of elongation ratio from three independent experiments was performed in Meta®Morph. Bars, 30 μm. The results are presented as the means ± SD (N = 3); *** p < 0.001.CC BY · PubMed Central
Figure 9 A schematic model of MRTF-induced snail expression via SP1 sites in EndMT.3.1. TGF-β stimulates the MRTFs’ upregulation in endothelial cells.
Figure 9 A schematic model of MRTF-induced snail expression via SP1 sites in EndMT.3.1. TGF-β stimulates the MRTFs’ upregulation in endothelial cells.CC BY · PubMed Central

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Metadata

Authors
Sobierajska, K., Ciszewski, W. M., Macierzynska-Piotrowska, E., Klopocka, W., Przygodzka, P., Karakula, M., Pestka, K., Wawro, M. E., & Niewiarowska, J.
Affiliations
  • Medical University of Lodz (PL)
  • Department of Molecular Cell Mechanisms, Medical University of Lodz, 92-215 Lodz, Poland
  • Department of Biochemistry and Cell Biology, Cardinal Stefan Wyszynski University in Warsaw, 01-938 Warsaw, Poland
  • Institute for Medical Biology (PL)
Corresponding author
  • Sobierajska, Katarzyna
  • Niewiarowska, Jolanta
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-08-16
Volume
21
Issue
16
Pages
5875
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21165875
PMC
PMC7461591
OpenAlex
W3049627893
Cited by
21
References
4
Citations by year
2026: 4 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 4
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Narodowe Centrum Badań i Rozwoju (MOMENTO Pol-Nor/209521/5/2013)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
Keywords
endothelial-to-mesenchymal transition, Snail transcription factor, MRTF, MRTF-A, MRTF-B, TGF-β1, TGF-beta2, metastasis, fibrosis
MeSH terms
Snail Family Transcription Factors, Cell Line, Humans, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcriptional Activation, Endothelial Cells, Epithelial-Mesenchymal Transition

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