Inhibition of BRD4 inhibits proliferation and promotes apoptosis of psoriatic keratinocytes.

Abstract

BACKGROUND:

Psoriasis is a common chronic recurrent inflammatory skin disease. The pathogenesis of psoriasis, such as other autoimmune diseases, is still unclear, which brings great difficulties to the treatment. This study aimed to investigate the role of bromine domain protein 4 (BRD4) in affecting the psoriatic keratinocytes.

METHODS:

Imiquimod-induced psoriasis mice model and TNF-α or IL-17A induced HaCAT cells, an experimental model in vitro for psoriasis, were constructed. The pathological skin changes at the back of mice were observed by hematoxylin and eosin (H&E) assay and evaluated by psoriasis area and severity index (PASI). KI67 expression and keratinocyte apoptosis at the skin tissues were, respectively, detected by Immunohistochemical analysis and TUNEL assay. The inflammatory factors in mice serum and culture supernatant were determined by ELISA assay. The related proteins expression of proliferation, apoptosis and MAPK pathway were detected by Western blot analysis.

RESULTS:

BRD4 expression was upregulated in injured skin on the back of imiquimod-induced mice and (+)-JQ1 relieved the skin injury by suppressing the inflammation and promoting apoptosis of keratinocytes. Consistently, BRD4 expression was also increased in TNF-α or IL-17A induced HaCAT cells. (+)-JQ1 suppressed the viability and inflammation, and promoted apoptosis of TNF-α or IL-17A induced HaCAT cells. In addition, the MAPK signaling pathway was inhibited by (+)-JQ1 whether in mice or HaCAT cells.

CONCLUSIONS:

Inhibition of BRD4 inhibited proliferation and inflammation and promoted apoptosis of psoriatic keratinocytes.

• Authors: Xiaohui Sun, Pengfei Yang
• Journal: Biomedical engineering online (Biomed Eng Online) Vol. 20 Issue 1 Pg. 107 (Oct 21 2021) ISSN: 1475-925X [Electronic] England
• PMID: 34674702 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Brd4 protein, mouse
• Nuclear Proteins
• Transcription Factors

Topics

• Animals
• Apoptosis
• Cell Proliferation
• Keratinocytes
• Mice
• Mice, Inbred BALB C
• Nuclear Proteins
• Psoriasis (chemically induced)
• Skin
• Transcription Factors