Downregulation of TNIP1 Expression Leads to Increased Proliferation of Human Keratinocytes and Severer Psoriasis-Like Conditions in an Imiquimod-Induced Mouse Model of Dermatitis
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{"title"=>"Downregulation of TNIP1 expression leads to increased proliferation of human keratinocytes and severer psoriasis-like conditions in an imiquimod-induced mouse model of dermatitis", "type"=>"journal", "authors"=>[{"first_name"=>"Yan", "last_name"=>"Chen", "scopus_author_id"=>"56702543900"}, {"first_name"=>"Heng", "last_name"=>"Yan", "scopus_author_id"=>"12801579600"}, {"first_name"=>"Zhiqiang", "last_name"=>"Song", "scopus_author_id"=>"36665202400"}, {"first_name"=>"Fangru", "last_name"=>"Chen", "scopus_author_id"=>"55844096300"}, {"first_name"=>"Huan", "last_name"=>"Wang", "scopus_author_id"=>"36605552800"}, {"first_name"=>"Jun", "last_name"=>"Niu", "scopus_author_id"=>"56606651100"}, {"first_name"=>"Xiaowei", "last_name"=>"Shi", "scopus_author_id"=>"56701342900"}, {"first_name"=>"Dongmei", "last_name"=>"Zhang", "scopus_author_id"=>"57145007800"}, {"first_name"=>"Na", "last_name"=>"Zhang", "scopus_author_id"=>"55842119800"}, {"first_name"=>"Zhifang", "last_name"=>"Zhai", "scopus_author_id"=>"35918054400"}, {"first_name"=>"Baiyu", "last_name"=>"Zhong", "scopus_author_id"=>"7102853625"}, {"first_name"=>"Liangjin", "last_name"=>"Cheng", "scopus_author_id"=>"56707890900"}, {"first_name"=>"Tian", "last_name"=>"Qian", "scopus_author_id"=>"56702088100"}, {"first_name"=>"Fei", "last_name"=>"Hao", "scopus_author_id"=>"56591777600"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203", "pmid"=>"26046540", "doi"=>"10.1371/journal.pone.0127957", "pui"=>"604911661", "issn"=>"19326203", "sgr"=>"84934946134", "scopus"=>"2-s2.0-84934946134"}, "id"=>"51b206bf-0675-3b6c-b897-bc644ef9f0c8", "abstract"=>"Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α-induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target.", "link"=>"http://www.mendeley.com/research/downregulation-tnip1-expression-leads-increased-proliferation-human-keratinocytes-severer-psoriasisl", "reader_count"=>11, "reader_count_by_academic_status"=>{"Researcher"=>6, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Researcher"=>6, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2098962"], "description"=>"<p>(A) Expression of <i>TNIP1</i> and CK6 mRNA levels based on qRT-PCR in the epidermis of psoriatic plaque of patients with moderate to severe plaque psoriasis (n = 12) and the epidermis of normal controls (n = 12). Data shown represent mean ± SD; (B) Expression of TNIP1 and CK6 protein levels based on Western blotting in psoriatic plaque (n = 4) and controls (n = 4) skin. Data shown represent mean ± SD. (C) Tissue sections obtained from patients with psoriasis (n = 8; panel b and panel c) or from healthy controls (n = 8; panel a) were stained with mice anti-TNIP1 antibody and counterstained with hematoxylin. Bar = 100 μm. Staining intensity was scored in a semiquantitative manner by two independent observers. Data are presented as mean staining intensity grade ± SEM. (D) The distribution of TNIP1 in HaCaT cells identified by immunofluorescence staining. Bar = 30 μm. *, p<0.05; **, p<0.01.</p>", "links"=>[], "tags"=>["TNIP 1 expression", "Blocking TNIP 1 expression", "modulating cancer cell growth", "ccaat", "phk", "GWAS", "TNIP 1", "tnf", "keratinocyte proliferation", "balb", "IMQ", "TNIP 1 shRNA", "TNIP 1 gene"], "article_id"=>1439271, "categories"=>["Biological Sciences"], "users"=>["Yan Chen", "Heng Yan", "Zhiqiang Song", "Fangru Chen", "Huan Wang", "Jun Niu", "Xiaowei Shi", "Dongmei Zhang", "Na Zhang", "Zhifang Zhai", "Baiyu Zhong", "Liangjin Cheng", "Tian Qian", "Fei Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127957.g001", "stats"=>{"downloads"=>4, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TNIP1_TNIP1_and_CK6_expression_in_psoriatic_lesions_/1439271", "title"=>"<i>TNIP1</i>/TNIP1 and CK6 expression in psoriatic lesions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-05 04:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2098963"], "description"=>"<p><b>Upregulation or downregulation of <i>TNIP1</i>/TNIP1 expression in HaCaT cells and the anti-proliferative effect of TNIP1 on HaCaT cells</b> (A) Green fluorescence observed in HaCaT cells stably infected by lentiviral particles respectively encoding rTNIP1, TNIP1 shRNA or a non-specific shRNA (control shRNA) as control. Bar = 100 μm. (B) mRNA expression levels of <i>TNIP1</i> in HaCaT cells confirmed by qRT-PCR. (C) The increase of TNIP1 in rTNIP1 infected HaCaT cells and the decrease of TNIP1 in shRNA infected HaCaT cells was confirmed by Western blotting. (D) Cell viability was assessed using the CCK-8 assay in rTNIP1, TNIP1 shRNA or control shRNA HaCaT cells. (E) HaCaT Cells stably infected with rTNIP1, TNIP1 shRNA, or control shRNA were assessed using the BrdU assay. (F, G) CK6 mRNA and protein levels were assessed by qRT-PCR and Western blotting, respectively, in rTNIP1, TNIP1 shRNA or control shRNA infected HaCaT cells. Data shown represent mean ± SD of three independent experiments performed in duplicates. *, p<0.05; **, p<0.01.</p>", "links"=>[], "tags"=>["TNIP 1 expression", "Blocking TNIP 1 expression", "modulating cancer cell growth", "ccaat", "phk", "GWAS", "TNIP 1", "tnf", "keratinocyte proliferation", "balb", "IMQ", "TNIP 1 shRNA", "TNIP 1 gene"], "article_id"=>1439272, "categories"=>["Biological Sciences"], "users"=>["Yan Chen", "Heng Yan", "Zhiqiang Song", "Fangru Chen", "Huan Wang", "Jun Niu", "Xiaowei Shi", "Dongmei Zhang", "Na Zhang", "Zhifang Zhai", "Baiyu Zhong", "Liangjin Cheng", "Tian Qian", "Fei Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127957.g002", "stats"=>{"downloads"=>3, "page_views"=>82, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Downregulation_of_TNIP1_Expression_Leads_to_Increased_Proliferation_of_Human_Keratinocytes_and_Severer_Psoriasis_Like_Conditions_in_an_Imiquimod_Induced_Mouse_Model_of_Dermatitis_Fig_2_/1439272", "title"=>"Downregulation of TNIP1 Expression Leads to Increased Proliferation of Human Keratinocytes and Severer Psoriasis-Like Conditions in an Imiquimod-Induced Mouse Model of Dermatitis - Fig 2", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-05 04:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2098964"], "description"=>"<p>(A) Green fluorescence observed in PHKs stably infected by lentiviral particles respectively encoding rTNIP1, TNIP1 shRNA or a non-specific shRNA (control shRNA). Bar = 100 μm. (B) Alteration of TNIP1 in PHKs is confirmed by Western blotting. PHKs stably infected with rTNIP1, TNIP1 shRNA, or control shRNA were assessed using (C) the CCK-8 assay, (D) the BrdU assay and (E) Western blotting (for CK6 protein level). Data are presented as mean ± SD of three independent experiments (*P<0.05 or **P<0.01 compared with control cells).</p>", "links"=>[], "tags"=>["TNIP 1 expression", "Blocking TNIP 1 expression", "modulating cancer cell growth", "ccaat", "phk", "GWAS", "TNIP 1", "tnf", "keratinocyte proliferation", "balb", "IMQ", "TNIP 1 shRNA", "TNIP 1 gene"], "article_id"=>1439273, "categories"=>["Biological Sciences"], "users"=>["Yan Chen", "Heng Yan", "Zhiqiang Song", "Fangru Chen", "Huan Wang", "Jun Niu", "Xiaowei Shi", "Dongmei Zhang", "Na Zhang", "Zhifang Zhai", "Baiyu Zhong", "Liangjin Cheng", "Tian Qian", "Fei Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127957.g003", "stats"=>{"downloads"=>9, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alteration_of_TNIP1_expression_in_PHKs_and_the_anti_proliferative_effect_of_TNIP1_on_PHKs_/1439273", "title"=>"Alteration of TNIP1 expression in PHKs and the anti-proliferative effect of TNIP1 on PHKs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-05 04:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2098965"], "description"=>"<p>(A) The interaction of TNIP1 and Erk2 in HaCaT cells was detected by Co-IP; (B) Downregulated TNIP1 resulted in the upregulation of p-Erk1/2 and C/EBPβ in HaCaT cells. (C) The pro-proliferative effect of downregulated TNIP1 in HaCaT cells was abrogated by U0126, an inhibitor of Erk1/2. TNIP1 shRNA HaCaT cells were cultured in the absence or presence of 20 μM U0126 (Beyotime, Shanghai, China) for 12 h. Dimethyl sulfoxide (DMSO) was used as control. Western blotting was performed to detect TNIP1, total Erk-1/2 (t-Erk1/2), phospho-Erk-1/2 (p-Erk1/2), C/EBPβ and CK6. (D) The pro-proliferative effect of downregulated TNIP1 in HaCaT cells was abrogated by C/EBPβ targeting siRNA. TNIP1 shRNA HaCaT cells were incubated in the absence or presence of 120 nM C/EBPβ targeting siRNA (Shanghai Genechem Co. Ltd.) for 8 h. A scrambled siRNA was used as control siRNA. Western blotting was performed to detect TNIP1, C/EBPβ and CK6 at 48 post-transfection. (E) Downregulated TNIP1 resulted in the upregulation of p-Erk1/2 and C/EBPβ in PHKs. Data are presented as mean ± SD of three independent experiments (*P<0.05 or **P<0.01 compared with control cells).</p>", "links"=>[], "tags"=>["TNIP 1 expression", "Blocking TNIP 1 expression", "modulating cancer cell growth", "ccaat", "phk", "GWAS", "TNIP 1", "tnf", "keratinocyte proliferation", "balb", "IMQ", "TNIP 1 shRNA", "TNIP 1 gene"], "article_id"=>1439274, "categories"=>["Biological Sciences"], "users"=>["Yan Chen", "Heng Yan", "Zhiqiang Song", "Fangru Chen", "Huan Wang", "Jun Niu", "Xiaowei Shi", "Dongmei Zhang", "Na Zhang", "Zhifang Zhai", "Baiyu Zhong", "Liangjin Cheng", "Tian Qian", "Fei Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127957.g004", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TNIP1_modulates_the_proliferation_of_keratinocytes_by_targeting_Erk1_2_and_C_EBP_946_/1439274", "title"=>"TNIP1 modulates the proliferation of keratinocytes by targeting Erk1/2 and C/EBPβ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-05 04:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2098966"], "description"=>"<p>(A) Red fluorescence observed in mice seven days after intradermal injections of lentiviral particles encoding TNIP1 shRNA or control shRNA, respectively. Blue arrows indicate the unspecific fluorescence of mice hair. The back of the mice had been shaved. (B) Western blotting was performed to verify that the TNIP1 expression level was decreased around the injection site. (C) Skin sections obtained seven days after injection from control shRNA mice (n = 4) or from TNIP1 shRNA mice (n = 4) were stained with rabbit anti-IκBα antibody, rabbit anti-TNFα antibody, rabbit anti-IL-1a antibody and rabbit anti-IL-1b antibody, respectively. Bar = 200 μm. Staining intensity was scored in a semiquantitative manner by two independent observers. Data are presented as mean staining intensity grade ± SEM. (D) Clinical scores of IMQ-induced psoriasis-like dermatitis in control shRNA or TNIP1 shRNA-injected mice at the indicated days with or without IMQ treatment. (E) H&E-stained sections of back skin from the mice at the indicated areas treated with or without IMQ. The epithelial layer (epi) is indicated by brackets. Green arrows indicate neutrophil infiltration and black arrows indicate parakeratosis. The epidermal layer thickness was more prominent, but unevenly distributed in TNIP1 shRNA-injected mice (panel b) compared with control shRNA-injected mice (panel c). No obvious epidermal hyperplasia was observed in TNIP1 shRNA-injected mice treated with topical emollient (the control, panel a). Bar = 100 μm. Data are presented as mean ± SD of three independent experiments (* P<0.05 or **P<0.01 compared with controls).</p>", "links"=>[], "tags"=>["TNIP 1 expression", "Blocking TNIP 1 expression", "modulating cancer cell growth", "ccaat", "phk", "GWAS", "TNIP 1", "tnf", "keratinocyte proliferation", "balb", "IMQ", "TNIP 1 shRNA", "TNIP 1 gene"], "article_id"=>1439275, "categories"=>["Biological Sciences"], "users"=>["Yan Chen", "Heng Yan", "Zhiqiang Song", "Fangru Chen", "Huan Wang", "Jun Niu", "Xiaowei Shi", "Dongmei Zhang", "Na Zhang", "Zhifang Zhai", "Baiyu Zhong", "Liangjin Cheng", "Tian Qian", "Fei Hao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127957.g005", "stats"=>{"downloads"=>2, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Downregulation_of_TNIP1_exaggerates_IMQ_induced_psoriasis_like_dermatitis_in_vivo_/1439275", "title"=>"Downregulation of TNIP1 exaggerates IMQ-induced psoriasis-like dermatitis <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-05 04:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2098974", "https://ndownloader.figshare.com/files/2098975", "https://ndownloader.figshare.com/files/2098976", "https://ndownloader.figshare.com/files/2098977", "https://ndownloader.figshare.com/files/2098978", "https://ndownloader.figshare.com/files/2098979"], "description"=>"<div><p>Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the <i>TNIP1</i> gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a <i>TNIP1</i> specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target.</p></div>", "links"=>[], "tags"=>["TNIP 1 expression", "Blocking TNIP 1 expression", "modulating cancer cell growth", "ccaat", "phk", "GWAS", "TNIP 1", "tnf", "keratinocyte proliferation", "balb", "IMQ", "TNIP 1 shRNA", "TNIP 1 gene"], "article_id"=>1439278, "categories"=>["Biological Sciences"], "users"=>["Yan Chen", "Heng Yan", "Zhiqiang Song", "Fangru Chen", "Huan Wang", "Jun Niu", "Xiaowei Shi", "Dongmei Zhang", "Na Zhang", "Zhifang Zhai", "Baiyu Zhong", "Liangjin Cheng", "Tian Qian", "Fei Hao"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0127957.s001", "https://dx.doi.org/10.1371/journal.pone.0127957.s002", "https://dx.doi.org/10.1371/journal.pone.0127957.s003", "https://dx.doi.org/10.1371/journal.pone.0127957.s004", "https://dx.doi.org/10.1371/journal.pone.0127957.s005", "https://dx.doi.org/10.1371/journal.pone.0127957.s006"], "stats"=>{"downloads"=>30, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Downregulation_of_TNIP1_Expression_Leads_to_Increased_Proliferation_of_Human_Keratinocytes_and_Severer_Psoriasis_Like_Conditions_in_an_Imiquimod_Induced_Mouse_Model_of_Dermatitis_/1439278", "title"=>"Downregulation of TNIP1 Expression Leads to Increased Proliferation of Human Keratinocytes and Severer Psoriasis-Like Conditions in an Imiquimod-Induced Mouse Model of Dermatitis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-05 04:48:52"}

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Relative Metric

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