TMT-based proteomics analysis reveals the protective effect of Jueyin granules on imiquimod-induced psoriasis mouse model by causing autophagy

Jiankun Song; Jingsi Jiang; Le Kuai; Yue Luo; Meng Xing; Ying Luo; Yi Ru; Xiaoying Sun; Huiping Zhang; Taiyi Liu; Xin Li; Bin Li

doi:10.1016/j.phymed.2021.153846

TMT-based proteomics analysis reveals the protective effect of Jueyin granules on imiquimod-induced psoriasis mouse model by causing autophagy

Phytomedicine. 2022 Feb:96:153846. doi: 10.1016/j.phymed.2021.153846. Epub 2021 Nov 6.

Authors

Jiankun Song¹, Jingsi Jiang², Le Kuai², Yue Luo¹, Meng Xing³, Ying Luo⁴, Yi Ru⁵, Xiaoying Sun⁴, Huiping Zhang⁶, Taiyi Liu⁶, Xin Li⁷, Bin Li⁸

Affiliations

¹ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
² Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
³ Department of Dermatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi`an, 710003, China.
⁴ Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
⁵ Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
⁶ Shanghai Applied Protein Technology Co., Ltd., Shanghai, 200233, China.
⁷ Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: 13661956326@163.com.
⁸ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Department of Dermatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi`an, 710003, China. Electronic address: 18930568129@163.com.

PMID: 34785109
DOI: 10.1016/j.phymed.2021.153846

Abstract

Background: Psoriasis is a chronic relapsing inflammatory skin disease that may markedly influence the patients' physical health and mental condition. According to animal models and clinical researches, it has been proved that Jueyin granules (JYG), a Chinese formula comprised of seven kinds of Traditional Chinese Medicine (TCM), is a therapeutic agent for treating psoriasis, while the specific mechanisms of the anti-inflammation effects of JYG have not been fully elucidated.

Objective: To uncover the underlying mechanisms of the action of JYG on psoriasis by proteomics clues.

Materials and methods: Differentially expressed proteins (DEPs) were explored by tandem mass tag (TMT)-based quantitative proteomics analysis after JYG treatment (administered intragastrically for 12 days). Bioinformatics analysis of DEPs was conducted through hierarchical clustering, volcano plot, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Major DEPs were further identified by enzyme-linked immunoassay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR).

Results: Ninety-five DEPs were identified, including 57 up-regulated and 38 down-regulated proteins, between imiquimod (IMQ) and IMQ+JYG groups. GO analysis indicated that DEPs were mainly associated with keratin filament, intermediate filament, extracellular exosome, extracellular space, innate immune response, keratinization, and keratinocyte differentiation. The KEGG pathway analysis manifested that estrogen signaling pathway, cholesterol metabolism, fat digestion, absorption, peroxisome proliferator-activated receptor (PPAR), and interleukin (IL)-17 signaling pathway might be the paramount pathways, through which JYG functioned on psoriasis. Furthermore, we determined that JYG could regulate macrophage and CD4+ T cell phenotypes by inducing autophagy.

Conclusions: JYG may induce autophagy by up-regulating ApoA1 and inhibit the infiltration of CD4+ T cells and macrophages, thereby alleviating IMQ-induced psoriatic inflammation.

Keywords: Autophagy; Jueyin granules (JYG); LC-MS/MS; Proteomics; Psoriasis.

MeSH terms

Animals
Autophagy
Disease Models, Animal
Humans
Imiquimod
Mice
Neoplasm Recurrence, Local
Proteomics*
Psoriasis* / chemically induced
Psoriasis* / drug therapy

Substances

Imiquimod