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

Document Type : Original Article

Authors

1 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

3 Trauma and Injury Research Center, Iran University of Medical Sciences, Tehran, Iran

4 Department of Dermatology, Rasoul-E Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran

5 Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Immunology, Erasmus Mc, University Medical Center, Rotterdam, The Netherlands

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.

Keywords

References

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