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  3. Topical application of phenformin ameliorates the psoriasis-like inflammatory response via the inhibition of c-Myc expression in keratinocytes

Topical application of phenformin ameliorates the psoriasis-like inflammatory response via the inhibition of c-Myc expression in keratinocytes

  • Biochem Biophys Res Commun. 2024 Aug 5:736:150503. doi: 10.1016/j.bbrc.2024.150503.
Xue Leng 1,  Shuangshuang Wang 2,  Dexuan Zhuang 3,  Tengfei Feng 4,  Xinyu Jiang 5,  Suling Xu 5,  Jing Guo 3,  Xunwei Wu 6
Affiliations

Affiliations

  • 1 Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430079, China.
  • 3 Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, Zhejiang, 315016, China.
  • 4 Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, Zhejiang, 315016, China.
  • 5 Department of Dermatology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China.
  • 6 Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Savaid Stomatology School, Hangzhou Medical College, Ningbo, Zhejiang, 315016, China. Electronic address: xunwei_2006@hotmail.com.
PMID: 39121669 DOI: 10.1016/j.bbrc.2024.150503
Abstract

Background: Psoriasis is a chronic inflammatory skin disease characterized by a complex pathogenesis involving various types of cells and cytokines. Among those, the pro-inflammatory cytokine IL-23/IL-17A axis plays a crucial role in the development and rapid progression of psoriasis. Phenformin, a derivative of metformin and a member of the biguanide class of drugs, exhibits superior anti-inflammatory and anti-tumor efficacy compared to metformin. However, the potential role of phenformin in anti-psoriatic skin inflammation has not been explored.

Methods: In this study, we utilized a mouse model of psoriasis and an in vitro model using human keratinocytes to investigate whether phenformin can suppress psoriasis-like inflammatory responses.

Results: Our results demonstrate that the topical application of phenformin significantly inhibited acute skin inflammatory responses in the psoriasis mouse model induced by imiquimod (IMQ). Additionally, phenformin suppressed the expression of psoriasis-related cytokines IL-17, IL-23, IL-8, and S100A8/S100A9 in an in vitro psoriatic keratinocyte model induced by IMQ. Furthermore, we found that IMQ-induced psoriatic skin and IMQ-treated keratinocytes exhibited high expression of the c-Myc gene, which was downregulated by phenformin. The c-Myc Inhibitor JQ1 similarly inhibited the psoriatic inflammatory response and the expression of psoriasis-related cytokines in both in vitro and in vivo models.

Conclusion: phenformin ameliorates the psoriasis-like inflammatory response by inhibiting c-Myc expression in keratinocytes, suggesting its potential as a topical drug for the treatment of psoriasis.

Keywords

Phenformin; Psoriasis; Skin inflammation; Topical application; c-Myc.

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