MicroRNA 181b Regulates Decorin Production by Dermal Fibroblasts and May Be a Potential Therapy for Hypertrophic Scar
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{"title"=>"MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar", "type"=>"journal", "authors"=>[{"first_name"=>"Peter", "last_name"=>"Kwan", "scopus_author_id"=>"35332512500"}, {"first_name"=>"Jie", "last_name"=>"Ding", "scopus_author_id"=>"56972998600"}, {"first_name"=>"Edward E.", "last_name"=>"Tredget", "scopus_author_id"=>"7005165745"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"603600345", "doi"=>"10.1371/journal.pone.0123054", "sgr"=>"84926442515", "scopus"=>"2-s2.0-84926442515", "pmid"=>"25837671"}, "id"=>"946c5d91-a691-3b50-994e-f971bfe3b87b", "abstract"=>"Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3' un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β1 induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.", "link"=>"http://www.mendeley.com/research/microrna-181b-regulates-decorin-production-dermal-fibroblasts-potential-therapy-hypertrophic-scar", "reader_count"=>14, "reader_count_by_academic_status"=>{"Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2004633"], "description"=>"<p>(a) Immunohistochemistry using a polyclonal goat anti-human DCN antibody and Alexa Fluor 488 secondary antibody (green fluorescence), and counterstained with DAPI (blue fluorescence) in representative site-matched sections of NS and HSc (scale bar = 50 μm). (b) Relative expression of DCN in matched superficial and deep NS and HSc sections was calculated from fluorescence using ImageJ (mean ± SEM, n = 4 patients, * P < 0.001).</p>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366778, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemical_DCN_expression_in_HSc_and_site_matched_NS_from_burn_patients_/1366778", "title"=>"Immunohistochemical DCN expression in HSc and site-matched NS from burn patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-02 16:23:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/2004634"], "description"=>"<p>Total RNA was extracted from SF and DF cell culture after 48 hours and relative expression of selected miRNA quantitated using RT-qPCR (mean ± SEM, n = 3, * P < 0.05).</p>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366779, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evidence_for_the_involvement_of_miRNA_in_DCN_downregulation_in_DF_/1366779", "title"=>"Evidence for the involvement of miRNA in <i>DCN</i> downregulation in DF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-02 16:23:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/2004636"], "description"=>"<p>Cells were cultured in DMEM + 2% FBS with the indicated treatment protocols and total RNA extracted for RT-qPCR. (a) Dose-response curve showing relative expression of miR-24 for SF and DF cultured in increasing concentrations of TGF-β<sub>1</sub> for 48 hours (mean ± SEM, n = 3). (b) Dose-response curve showing relative expression of miR-181b for SF and DF culutured in increasing concentrations of TGF-β<sub>1</sub> for 48 hours (mean ± SEM, n = 3, * P < 0.05, ** P < 0.01). (c) Time-response curve showing relative expression of miR-181b for SF and DF at fixed concentrations of TGF-β<sub>1</sub> (SF 10 ng/mL, DF 20 ng/mL) (mean ± SEM, n = 3, * P < 0.03).</p>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366781, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regulation_of_miRNA_expression_by_TGF_1_in_SF_and_DF_/1366781", "title"=>"Regulation of miRNA expression by TGF-β<sub>1</sub> in SF and DF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-02 16:23:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/2004638"], "description"=>"<p>Total RNA was extracted from tissue specimens using a chilled pestle and mortar and Trizol for relative quantitation using RT-qPCR. (a) Relative expression of miR-181b in matched superficial and deep dermis of NS (mean ± SEM, n = 3 samples per patient, * P < 0.001). (b) Relative expression of miR-181b in matched NS and HSc (mean ± SEM, n = 3 samples per patient, * P < 0.05, ** P < 0.01).</p>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366783, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_expression_of_miR_181b_in_matched_superficial_and_deep_dermis_and_site_matched_NS_and_HSc_biopsies_/1366783", "title"=>"Relative expression of miR-181b in matched superficial and deep dermis and site-matched NS and HSc biopsies.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-02 16:23:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/2004640"], "description"=>"<p>HEK293A were cultured in DMEM + 2% FBS and transfected with pmirGLO constructs containing various miRNA binding sites and (a) relative fluorescence quantitated using a luminometer to determine relative knockdown by miR-181b (mean ± SEM, n = 4, *** P ≤ 0.01). SF were cultured in DMEM + 2% FBS and transfected with miR-control, synthetic miR-181b or siRNA-DCN and (b) DCN protein in supernatant was measured by ELISA (mean ± SEM, n = 3, ** P < 0.03), and (c) DCN mRNA was measured using RT-qPCR on total RNA (mean ± SEM, n = 3, * P < 0.05). (d) DF were cultured in DMEM + 2% FBS and transfected with antagomiR-control (amiR-control) or antagomiR-181b (amiR-181b) and DCN protein in supernatant was measured by ELISA (mean ± SEM, n = 3, *** P < 0.01).</p>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366785, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regulation_of_DCN_by_miR_181b_/1366785", "title"=>"Regulation of DCN by miR-181b.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-02 16:23:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/2004641"], "description"=>"<p>(a) antagomiR-181b reversed DCN downregulation in HSc fibroblasts. Cells were stimulated by TGF-β1 at indicated concentrations and transfected with antagomiR-control or antagomiR-181b for 48 hours in DMEM + 2% FBS, and DCN protein was measured using ELISA on the supernatants (mean ± SEM, n = 3, * P < 0.02, ** P < 0.006). (b) antagomiR-181b reversed myofibroblast differentiation in HSc fibroblasts. Cells were stimulated by TGF-β1 10 ng/mL and transfected with antagomiR-control or antagomiR-181b for 48 hours in DMEM + 2% FBS then permeabilized and stained for α-smooth muscle actin and 10 000 cells per sample measured by flow cytometry (mean ± SEM, n = 3, *** P <0.03).</p>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366786, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_antagomiR_181b_on_TGF_946_1_stimulated_NS_and_HSc_fibroblasts_/1366786", "title"=>"The effect of antagomiR-181b on TGF-β1 stimulated NS and HSc fibroblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-02 16:23:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/2004647", "https://ndownloader.figshare.com/files/2004648", "https://ndownloader.figshare.com/files/2004649", "https://ndownloader.figshare.com/files/2004651", "https://ndownloader.figshare.com/files/2004652", "https://ndownloader.figshare.com/files/2004653"], "description"=>"<div><p>Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3’ un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β<sub>1</sub> stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β<sub>1</sub> induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.</p></div>", "links"=>[], "tags"=>["increase decorin protein expression", "mir", "hypertrophic scar fibroblasts", "fibroblasts downregulate decorin", "MicroRNA 181 b Regulates Decorin Production", "hypertrophic scar", "tgf", "microrna", "Hypertrophic Scar Hypertrophic scarring"], "article_id"=>1366792, "categories"=>["Biological Sciences"], "users"=>["Peter Kwan", "Jie Ding", "Edward E. Tredget"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0123054.s001", "https://dx.doi.org/10.1371/journal.pone.0123054.s002", "https://dx.doi.org/10.1371/journal.pone.0123054.s003", "https://dx.doi.org/10.1371/journal.pone.0123054.s004", "https://dx.doi.org/10.1371/journal.pone.0123054.s005", "https://dx.doi.org/10.1371/journal.pone.0123054.s006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MicroRNA_181b_Regulates_Decorin_Production_by_Dermal_Fibroblasts_and_May_Be_a_Potential_Therapy_for_Hypertrophic_Scar_/1366792", "title"=>"MicroRNA 181b Regulates Decorin Production by Dermal Fibroblasts and May Be a Potential Therapy for Hypertrophic Scar", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-04-02 16:23:35"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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