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CTNNBIP1 modulates keratinocyte differentiation through promoting the transcription of β-catenin/TCF-complex downstream genes
Zhibo Yang
the Second Affiliated Hospital of Hunan University of Chinese Medicine
Corresponding Author
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Background: During psoriasis initiation and development, deregulations in signaling pathways and gene expression are observed.
Methods: Herein, we downloaded seven sets of microarray mRNA expression profiles showing differentially-expressed genes in psoriasis lesion skin and non-lesion skin tissues and three sets of RNA-seq data and analyzed these online data attempting to screen for crucial genes related to keratinocyte differentiation and psoriasis development.
Results: The expression of catenin beta interacting protein 1 (CTNNBIP1) was remarkably downregulated within psoriasis lesion skin tissue samples compared to that within non-lesion skin tissues based on both online data and experimental results. In response to a period of different therapies, respectively, CTNNBIP1 expression could be rescued in lesion skin tissues. Within IMQ-induced psoriasis-like dermatitis in mice, CTNNBIP1 silence further aggravated psoriatic phenotypes. In human immortalized keratinocytes, HaCaT cells, CTNNBIP1 silence significantly inhibited cell apoptosis and promoted cell proliferation. Regarding the molecular mechanism, CTNNBIP1 silence in HaCaT cells promoted β-catenin nucleus translocation, enhanced the transcriptional activity of TCF4, and increased β-catenin/TCF-complex downstream c-Myc and cyclin D1 proteins while decreased the late differentiation marker filaggrin. In contrast to CTNNBIP1, the expression of c-Myc and cyclin D1 showed to be dramatically upregulated within psoriasis lesion tissue samples than that within non-lesion tissue samples. Within tissues, c-Myc and cyclin D1 showed to be negatively correlated with CTNNBIP1, respectively.
Conclusions: We identify CTNNBIP1 as an abnormally downregulated gene in psoriasis. CTNNBIP1 silence significantly disturbs the differentiation of keratinocytes through promoting the transcription of β-catenin/TCF-complex downstream genes.
Keywords
psoriasis, CTNNBIP1, keratinocyte differentiation, β-catenin/TCF-complex, c-Myc, cyclin D1
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Research
CTNNBIP1 modulates keratinocyte differentiation through promoting the transcription of β-catenin/TCF-complex downstream genes
Zhibo Yang
the Second Affiliated Hospital of Hunan University of Chinese Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 31 Dec, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cell Communication and Signaling
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: During psoriasis initiation and development, deregulations in signaling pathways and gene expression are observed.
Methods: Herein, we downloaded seven sets of microarray mRNA expression profiles showing differentially-expressed genes in psoriasis lesion skin and non-lesion skin tissues and three sets of RNA-seq data and analyzed these online data attempting to screen for crucial genes related to keratinocyte differentiation and psoriasis development.
Results: The expression of catenin beta interacting protein 1 (CTNNBIP1) was remarkably downregulated within psoriasis lesion skin tissue samples compared to that within non-lesion skin tissues based on both online data and experimental results. In response to a period of different therapies, respectively, CTNNBIP1 expression could be rescued in lesion skin tissues. Within IMQ-induced psoriasis-like dermatitis in mice, CTNNBIP1 silence further aggravated psoriatic phenotypes. In human immortalized keratinocytes, HaCaT cells, CTNNBIP1 silence significantly inhibited cell apoptosis and promoted cell proliferation. Regarding the molecular mechanism, CTNNBIP1 silence in HaCaT cells promoted β-catenin nucleus translocation, enhanced the transcriptional activity of TCF4, and increased β-catenin/TCF-complex downstream c-Myc and cyclin D1 proteins while decreased the late differentiation marker filaggrin. In contrast to CTNNBIP1, the expression of c-Myc and cyclin D1 showed to be dramatically upregulated within psoriasis lesion tissue samples than that within non-lesion tissue samples. Within tissues, c-Myc and cyclin D1 showed to be negatively correlated with CTNNBIP1, respectively.
Conclusions: We identify CTNNBIP1 as an abnormally downregulated gene in psoriasis. CTNNBIP1 silence significantly disturbs the differentiation of keratinocytes through promoting the transcription of β-catenin/TCF-complex downstream genes.
Figure 2
Figure 4
Figure 5
Figure 7
Figure 9
Figure 11
Figure 13