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

Abstract

Objective: Psoriasis is a common, auto-immune skin disease characterized by abnormal proliferation and differentiationof keratinocytes. Studies revealed the role of stress stimulators in the pathogenesis of psoriasis. Oxidative stressand heat shock are two important stress factors tuning differentiation and proliferation of keratinocytes, regardingto psoriasis disease. BCL11B is a transcription factor with critical role in embryonic keratinocyte differentiation andproliferation. 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-relatedkeratinocyte stress factors.Materials and Methods: In this experimental study, data sets of psoriatic and healthy skin samples were downloadedin silico and BCL11B was chosen as a potential transcription factor to analyze. Next, a synchronized in vitro model wasdesigned for keratinocyte proliferation and differentiation. Oxidative stress and heat shock treatments were employed onHaCaT keratinocytes in culture, and BCL11B expression level was measured. Cell proliferation rate and differentiationwere analyzed by synchronized procedure test. Flow cytometry was done to analyze cell cycle alterations due to theoxidative stress.Results: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) data revealed a significantupregulation of BCL11B expression in keratinocytes, by 24 hours after initiating differentiation. However, it was followedby a significant down-regulation in almost all the experiments, including the synchronized model. Flow cytometer datademonstrated 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

• bcl11b
• keratinocyte
• psoriasis
• stress-induced differentiation
• transcription factor