BCL11B Is Involved in Stress-Induced Differentiation of Keratinocytes and Has A Potential Role in Psoriasis Pathogenesis

Sara Parsa, Zahra Soheila Soheili*, Hamidreza Alizadeh Otaghvar, Elham Behrangi, Parvin Mansouri, Erik Lubberts, Seyed Javad Mowla*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objective: Psoriasis is a common, auto-immune skin disease characterized by abnormal proliferation and differentiation of keratinocytes. Studies revealed the role of stress stimulators in the pathogenesis of psoriasis. Oxidative stress and heat shock are two important stress factors tuning differentiation and proliferation of keratinocytes, regarding to psoriasis disease. BCL11B is a transcription factor with critical role in embryonic keratinocyte differentiation and proliferation. Given this, in keratinocytes we have investigated potential role of BCL11B in stress-induced differentiation. Furthermore, we searched for a potential intercommunication between BCL11B expression and psoriasis-related keratinocyte stress factors. Materials and Methods: In this experimental study, data sets of psoriatic and healthy skin samples were downloaded in silico and BCL11B was chosen as a potential transcription factor to analyze. Next, a synchronized in vitro model was designed for keratinocyte proliferation and differentiation. Oxidative stress and heat shock treatments were employed on HaCaT keratinocytes in culture, and BCL11B expression level was measured. Cell proliferation rate and differentiation were analyzed by synchronized procedure test. Flow cytometry was done to analyze cell cycle alterations due to the oxidative stress. Results: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) data revealed a significant upregulation of BCL11B expression in keratinocytes, by 24 hours after initiating differentiation. However, it was followed by a significant down-regulation in almost all the experiments, including the synchronized model. Flow cytometer data demonstrated a G1 cell cycle arrest in the treated cells. Conclusion: Results indicated a remarkable role of BCL11B in differentiation and proliferation of HaCaT keratinocytes. This data along with the results of flow cytometer suggested a probable role for BCL11B in stress-induced differentiation, which is similar to what is happening during initiation and progression of normal differentiation.

Original languageEnglish
Pages (from-to)300-306
Number of pages7
JournalCell Journal
Volume25
Issue number5
DOIs
Publication statusPublished - May 2023

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© 2023 Royan Institute (ACECR). All rights reserved.

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