The Effects of Hedgehog on the RNA-Binding Protein Msi1 in the Proliferation and Apoptosis of Mesenchymal Stem Cells
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{"title"=>"The Effects of Hedgehog on the RNA-Binding Protein Msi1 in the Proliferation and Apoptosis of Mesenchymal Stem Cells", "type"=>"journal", "authors"=>[{"first_name"=>"In Sun", "last_name"=>"Hong", "scopus_author_id"=>"15074102100"}, {"first_name"=>"Kyung Sun", "last_name"=>"Kang", "scopus_author_id"=>"57092959400"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84873899390", "doi"=>"10.1371/journal.pone.0056496", "issn"=>"19326203", "pui"=>"368342688", "pmid"=>"23418578", "scopus"=>"2-s2.0-84873899390"}, "id"=>"00ed8add-c951-382e-9d81-65dd7650abff", "abstract"=>"Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are essential tools for regenerative medicine due to their capacity for self-renewal and multi-lineage differentiation. As MSCs are found in very small numbers in various tissues, in vitro cell expansion is an essential step that is needed before these cells can be used in clinical applications. Therefore, it is important to identify and characterize factors that are involved in MSC proliferation and apoptosis. In the present study, we focused on Hedgehog (Hh) signaling because several studies have proposed that Hh signaling plays a critical role in controlling the proliferation of stem and progenitor cells. However, the molecular mechanisms underlying the effects on the proliferation and apoptosis of MSCs remain unclear. In this study, we evaluated the direct effects of Hh signaling on the proliferation and apoptosis of hUCB-MSCs as well as investigated potential downstream regulatory mechanisms that may be responsible for Hh signaling. We observed that the Hedgehog agonist purmorphamine enhanced cell proliferation and suppressed apoptosis through the RNA-binding protein Msi1 by regulating the expression of an oncoprotein (i.e., c-Myc), a cell cycle regulatory molecule (i.e., p21(CIP1,WAF1)) and two microRNAs (i.e., miRNA-148a and miRNA-148b). This study provides novel insights into the molecular mechanisms regulating the self-renewal capability of MSCs with relevance to clinical applications.", "link"=>"http://www.mendeley.com/research/effects-hedgehog-rnabinding-protein-msi1-proliferation-apoptosis-mesenchymal-stem-cells", "reader_count"=>15, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>3, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/490934"], "description"=>"<p>The Hedgehog agonist purmorphamine enhanced cell proliferation and suppressed apoptosis through the RNA-binding protein Msi1 by regulating the expression of an oncoprotein (i.e., c-Myc), a cell cycle regulatory molecule (i.e., p21<sup>CIP1,WAF1</sup> ) and two miRNAs (i.e., miRNA-148a and miRNA-148b).</p>", "links"=>[], "tags"=>["schematic", "diagram", "hedgehog", "signaling", "cascade", "regulates", "apoptosis", "proliferation"], "article_id"=>161453, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g009", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_schematic_diagram_showing_the_proposed_Hedgehog_signaling_cascade_that_regulates_the_apoptosis_and_proliferation_of_MSCs_/161453", "title"=>"A schematic diagram showing the proposed Hedgehog signaling cascade that regulates the apoptosis and proliferation of MSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:34:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/490613"], "description"=>"<p>hUCB-MSCs and hDFs were incubated in standard culture medium with or without 4 µM purmorphamine for 3 days. p21<sup>CIP1,WAF1</sup> and c-Myc expressions levels were then assessed by western blotting. Purmorphamine treatment decreased and increased the expression of p21<sup>CIP1,WAF1</sup> (<b>A</b>) and c-Myc (<b>B</b>), respectively. After preculture for 24 h, hUCB-MSCs were transfected with 50 nM Msi1 siRNA for 48 h. The transfection of 50 nM Msi1 siRNA significantly increased and decreased the expression levels of p21<sup>CIP1,WAF1</sup> (<b>C</b>) and c-Myc (<b>D</b>), respectively. β-actin was used as an internal control. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["purmorphamine", "msi1", "knockdown", "c-myc"], "article_id"=>161143, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g005", "stats"=>{"downloads"=>4, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_purmorphamine_and_Msi1_knockdown_on_p21_CIP1_WAF1_and_c_Myc_expression_/161143", "title"=>"The effects of purmorphamine and Msi1 knockdown on p21<sup>CIP1,WAF1</sup> and c-Myc expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:32:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/490870"], "description"=>"<p>hUCB-MSCs were first transfected with 50 nM Msi1 siRNA for 48 h and then treated with or without 4 µM purmorphamine for 3 days. The expression profiles of the miRNAs were then analyzed using real-time PCR. Purmorphamine treatment attenuated the stimulatory effects of Msi1 knockdown on miR-148a (<b>A</b>) and miR-148b (<b>B</b>) expression. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["purmorphamine", "mir-148a", "mir-148b", "mediated"], "article_id"=>161393, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g008", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_purmorphamine_on_miR_148a_and_miR_148b_are_mediated_through_Msi1_/161393", "title"=>"The effects of purmorphamine on miR-148a and miR-148b are mediated through Msi1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:33:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/490736"], "description"=>"<p>hUCB-MSCs were first transfected with 50 nM Msi1 siRNA for 48 h and then treated with or without purmorphamine (4 µM) for 3 days. The transfection of 50 nM Msi1 siRNA reversed the inhibitory (<b>A</b>) and stimulatory (<b>B</b>) effects of purmorphamine on p21<sup>CIP1,WAF1</sup> and c-Myc expression, respectively. β-actin was used as an internal control. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["purmorphamine", "c-myc", "mediated"], "article_id"=>161262, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g006", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_purmorphamine_on_p21_CIP1_WAF1_and_c_Myc_are_mediated_through_Msi1_/161262", "title"=>"The effects of purmorphamine on p21<sup>CIP1,WAF1</sup> and c-Myc are mediated through Msi1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:33:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/490801"], "description"=>"<p>hUCB-MSCs were treated with 4 µM purmorphamine for 3 days or transfected with 50 nM Msi1 siRNA, and then, the expression profiles of the miRNAs were analyzed by real-time PCR. The expression levels of miR-148a (<b>A</b>) and miR-148b (<b>B</b>) were decreased by purmorphamine treatment. The transfection of 50 nM Msi1 siRNA increased the expression levels of miR-148a (<b>C</b>) and miR-148b (<b>D</b>). The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["purmorphamine", "msi1", "knockdown", "mir-148a", "mir-148b"], "article_id"=>161323, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g007", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_purmorphamine_and_Msi1_knockdown_on_miR_148a_and_miR_148b_expression_/161323", "title"=>"The effects of purmorphamine and Msi1 knockdown on miR-148a and miR-148b expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:33:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/490341"], "description"=>"<p>hUCB-MSCs were cultured in serum-free medium and then treated with or without purmorphamine (4 µM). Apoptotic levels were assessed with a TUNEL assay and western blotting. Apoptotic cells were quantified by counting the number of TUNEL-positive cells. Purmorphamine treatment for 72 h significantly decreased the number of TUNEL-positive cells (<b>A</b>) and the expression level of cleaved caspase-3 (<b>B</b>). The blue staining (DAPI) identifies cell nuclei. (<b>C</b>) The expression level of Msi1 was assessed by western blot. 4 µM purmorphamine treatment for 72 h significantly increased Msi1 expression. β-actin was used as an internal control. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["stimulation", "suppresses", "apoptosis", "activation"], "article_id"=>160869, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g002", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hedgehog_stimulation_suppresses_apoptosis_through_the_activation_of_Msi1_/160869", "title"=>"Hedgehog stimulation suppresses apoptosis through the activation of Msi1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:30:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/490507"], "description"=>"<p>Cells were treated with or without 4 µM purmorphamine and transfected with or without 50 nM Msi1 siRNA. The cell proliferation levels were then evaluated by direct cell counting, and apoptosis levels were assessed with a TUNEL assay and western blotting. Purmorphamine increased cell proliferation (<b>A</b>) and decreased TUNEL-positive cell numbers (<b>B</b>), while the 50 nM Msi1 siRNA transfection produced the opposite effects. The knockdown of Msi1 attenuated the above effects of purmorphamine treatment. The blue staining (DAPI) identifies cell nuclei. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["attenuating", "msi1", "knockdown", "hh", "signaling", "msc", "proliferation"], "article_id"=>161029, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_attenuating_effects_of_Msi1_knockdown_on_Hh_signaling_in_MSC_proliferation_and_apoptosis_/161029", "title"=>"The attenuating effects of Msi1 knockdown on Hh signaling in MSC proliferation and apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:31:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/490238"], "description"=>"<p>hUCB-MSCs and hDFs were incubated in standard culture medium with or without purmorphamine (4 µM). Cell numbers were then obtained by direct cell counting with a hemocytometer. (<b>A</b>) Purmorphamine exposure significantly increased MSC proliferation in a dose-dependent manner compared to negative controls. (<b>B</b>) Purmorphamine treatment did not affect cell proliferation in hDFs compared to negative controls. (<b>C, D</b>) After preculture for 24 h, protein and mRNA were isolated from human dermal fibroblasts (hDFs) and hUCB-MSCs. The level of Hh expression was assessed by western blotting, and Patched-1 mRNA levels were assessed by real-time PCR. The relative expression levels of Hh and Patched-1 in hUCB-MSCs were higher than the levels observed in hDFs. β-actin was used as an internal control. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["hedgehog", "agonist", "purmorphamine", "proliferation"], "article_id"=>160758, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Hedgehog_agonist_purmorphamine_specifically_promotes_the_proliferation_of_MSCs_/160758", "title"=>"The Hedgehog agonist purmorphamine specifically promotes the proliferation of MSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:30:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/490431"], "description"=>"<p>After preculture for 24 h, hUCB-MSCs were transfected with 50 nM Msi1 siRNA for 48 h. The transfection of 50 nM Msi1 siRNA efficiently reduced Msi1 protein levels. The transfection of 50 nM Msi1 siRNA also significantly increased the number of TUNEL-positive cells (<b>A</b>), as well as the expression level of activated caspase-3 (<b>B</b>), compared with the controls. (<b>C</b>) The transfection of 50 nM Msi1 siRNA significantly increased cell proliferation compared to controls. The blue staining (DAPI) identifies cell nuclei. β-actin was used as an internal control. The results are shown as the mean ± SD from three independent experiments. * P<0.05, ** P<0.01, and *** P<0.001.</p>", "links"=>[], "tags"=>["msi1", "knockdown", "proliferation"], "article_id"=>160959, "categories"=>["Biochemistry", "Cell Biology", "Developmental Biology"], "users"=>["In-Sun Hong", "Kyung-Sun Kang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0056496.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_Msi1_knockdown_on_cell_proliferation_and_apoptosis_/160959", "title"=>"The effects of Msi1 knockdown on cell proliferation and apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:31:23"}

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Relative Metric

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