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Article Publish Status: FREE
Abstract Title:

Berberine downregulates CDC6 and inhibits proliferation via targeting JAK-STAT3 signaling in keratinocytes.

Abstract Source:

Cell Death Dis. 2019 Mar 20 ;10(4):274. Epub 2019 Mar 20. PMID: 30894513

Abstract Author(s):

Shuna Sun, Xiaojie Zhang, Mengru Xu, Fang Zhang, Fei Tian, Jianfeng Cui, Yangyang Xia, Chenxi Liang, Shujie Zhou, Haifeng Wei, Hui Zhao, Guojing Wu, Bohan Xu, Xiaochen Liu, Guanqun Yang, Qinzhou Wang, Lei Zhang, Yaoqin Gong, Changshun Shao, Yongxin Zou

Article Affiliation:

Shuna Sun

Abstract:

Psoriasis is a chronic skin disease characterized by hyperproliferation and impaired differentiation of epidermal keratinocytes accompanied by increased inflammation, suggesting that molecules with antiproliferation and anti-inflammatory abilities may be effective for its treatment. One of the key steps in regulating cell proliferation is DNA replication initiation, which relies on prereplication complex (pre-RC) assembly on chromatin. CDC6 is an essential regulator of pre-RC assembly and DNA replication in eukaryotic cells, but its role in proliferation of keratinocytes and psoriasis is unknown. Here we examined CDC6 expression in psoriatic skin and evaluated its function in the proliferation of human keratinocytes. CDC6 expression is upregulated in epidermal cells in psoriatic lesions and it could be induced by IL-22/STAT3 signaling, a key signaling pathway involved in the pathogenesis of psoriasis, in keratinocytes. Depletion of CDC6 leads to decreased proliferation of keratinocytes. We also revealed that berberine (BBR) could inhibit CDK4/6-RB-CDC6 signaling in keratinocytes, leading to reduced proliferation of keratinocytes. The mechanism of antiproliferation effects of BBR is through the repression of JAK1, JAK2, and TYK2, which in turn inhibits activation of STAT3. Finally, we demonstrated that BBR could inhibit imiquimod-induced psoriasis-like skin lesions and upregulation of CDC6 and p-STAT3 in mice. Collectively, our findings indicate that BBR inhibits CDC6 expression and proliferation in human keratinocytes by interfering the JAK-STAT3 signaling pathway. Thus, BBR may serve as a potential therapeutic option for patients with psoriasis.

Study Type : Human In Vitro
Additional Links
Pharmacological Actions : Antiproliferative : CK(6801) : AC(5032)

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Sayer Ji
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