Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via Phosphoinositide 3-Kinase/Akt Pathways

Li, Changji; Xiao, Lei; Jia, Jinjing; Fan, Li; Wang, Xin; Duan, Qiangde; Jing, Huiling; Yang, Pei-Wen; Chen, Caifeng; Wang, Qiong; Liu, Jiankang; Shao, Yongping; Wang, Nanping; Zheng, Yan

doi:10.1016/j.jid.2018.06.184

Cited by 50 publications

(50 citation statements)

References 29 publications

(34 reference statements)

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“…However, the effects of daphnetin on keratinocytes proliferation and inflammatory response are still not clear. The cocktail of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokines were used to simulate keratinocytes to establish psoriatic keratinocyte model in vitro [18][19][20]. In the current study, M5 (2.5 ng/ ml) simulation was found to be able to induce HaCaT keratinocytes manifesting some features of psoriatic keratinocytes (Fig.…”

Section: Discussionmentioning

confidence: 67%

“…The mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokines were used to simulate HaCaT keratinocytes to establish psoriatic keratinocyte model recapitulating some features of psoriasis in vitro [18][19][20]. M5 (2.5 ng/ml) stimulation for 72 h and 96 h significantly promoted proliferation of HaCaT keratinocytes ( Fig.…”

Section: M5 Stimulation Promoted Cell Proliferation and Inflammatory mentioning

confidence: 99%

“…The cocktail of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokines induces keratinocytes manifesting some features of psoriatic keratinocyte in vitro [18]. Therefore, M5 cytokines cocktail was used to establish psoriatic keratinocyte model in vitro [19][20][21]. Imiquimod (IMQ), an agonist of Toll-like receptor 7/8 ligand, induced a dermatitis in mice closely resembling human psoriasis [22].…”

Section: Introductionmentioning

confidence: 99%

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Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

et al. 2020

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Background Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyperproliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. Methods HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. Results Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. Conclusions Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

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Section: Discussionmentioning

confidence: 67%

Section: M5 Stimulation Promoted Cell Proliferation and Inflammatory mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

et al. 2020

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“…The psoriasis-like cell model was established as previously described (15,16). HaCaT cells were seeded in cell plates at appropriate densities, and after 12 hours of culture, the cells were stimulated with 10 ng/ml M5, a cocktail of inflammatory cytokines including IL-17A (cat no.200-17, Peprotech, USA), IL-22 (cat no.200-22, Peprotech, USA), IL-1a (cat no.200-01A, Peprotech, USA), oncostatin M (cat no.300-10H, Peprotech, USA), and TNF-a (cat no.300-01A, Peprotech, USA) for 24-48 hours before collection for the next experiment.…”

Section: Pro-inflammatory Cytokines-induced Psoriasis-like Cell Modelmentioning

confidence: 99%

RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior

Zeng

Zhang

et al. 2021

Front. Immunol.

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BackgroundKeratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.ObjectivesWe investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.MethodsWe examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.ResultsWe showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.ConclusionsThese findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.

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“…CK1/10 are markers for keratinised epithelium and CK4/13 can be used as markers of non-keratinised epithelium [28]. CRNN is believed to be a marker of keratinocyte proliferation [29]. CK19 expression has been reported in dysfunctional oral epithelial differentiation [30,31] and a biomarker of highly invasive oral squamous cell carcinoma with metastatic potential [32].…”

Section: Discussionmentioning

confidence: 99%

Expression of cornulin in tongue squamous cell carcinoma

Saleem¹,

Aleem²,

Atiq³

et al. 2021

ecancer

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The aim of the study is to identify cornulin (CRNN) protein expression associated with advancement of tongue squamous cell carcinoma (TSCC). A comparison of addictive (containing potential carcinogens) versus non-addiction causative agents was expected to allow detection of differences in CRNN expression associated with TSCC. Bespoke tissue microarrays (TMAs) were prepared and immunohistochemistry (IHC) performed to determine the changes in CRNN expression in epithelial cells of node-negative (pN-), node-positive (pN +) TSCC and non-cancer patients' oral tissues. TMAs were validated by performing IHC on whole diagnostic tissues. Chi-square test or Fisher's-exact tests were used to establish significant expression differences. Analogous analyses were performed for biomarkers previously associated with TSCC, namely collagen I alpha 2 (COL1A2) and decorin (DCN) to compare the significance of CRNN. Keratinisation and its level (low, extensive) were studied in relation to CRNN so that the extent of squamous differentiation could better be assessed. IHC immunoreactive score (IRS) clustered the patients based on weak/moderate (Low (IRS ≤ +3)) or strong (High (IRS ≥ +4)) expression groups. A low expression was observed in a larger number of patients in control proteins COL1A2 (77.3%), DCN (87.5%) and target protein CRNN (52.3%), respectively. Low CRNN expression was observed in TSCC where nodes were involved (pN+: mean 1.4 ± 2.1) (p = 0.248). Keratinisation (%) was low (0% ≤ 50%) in 42.2% and extensive (1% ≥ 50.0%) in 57.8% patients. In conclusion, our study suggested that Low CRNN expression was associated with grade and lymph node metastasis in TSCC. CRNN expression is independent of addiction, however potentially carcinogenic addictive substances might be aiding in the disease progression.

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Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via Phosphoinositide 3-Kinase/Akt Pathways

Cited by 50 publications

References 29 publications

Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior

Expression of cornulin in tongue squamous cell carcinoma

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