Transcriptomic Analysis of the Mechanisms for Alleviating Psoriatic Dermatitis Using Taodan Granules in an Imiquimod-Induced Psoriasis-like Mouse Model


doi: 10.3389/fphar.2021.632414.


eCollection 2021.

Affiliations

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Le Kuai et al.


Front Pharmacol.


.

Abstract

Taodan granules (TDGs) are clinically efficacious for treating psoriasis, buttheir specific mechanisms of action are unclear. In this study, we determined the concentrations of tanshinone IIA and curcumol using high-performance liquid chromatography (HPLC) to establish quality control parameters for assessing the mechanism of TDGs in treating psoriasis. Thereafter, a mouse model of psoriasis was treated with TDGs. TDGs attenuated imiquimod-induced typical erythema, scales, and thickening of the back and ear lesions in the psoriatic mouse model. Furthermore, PCNA and Ki67-positive cells were reduced in the epidermis of psoriatic lesions following TDG treatment. Finally, the sequencing results were verified using a multitude of methods, and the mechanism of action of TDGs against psoriasis was found to be via the upregulation of metabolic signaling pathways such as the Gly-Ser-Thr axis, the downregulation of immune and inflammatory pathways, and the decrease in Rac2 and Arhgdib concentrations. Overall, this study clarified the mechanism of TDG treatment for psoriasis and provided evidence for its clinical application.


Keywords:

Chinese medicine; RNA sequencing analysis; psoriasis; taodan granules; transcriptomic analysis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures


FIGURE 1



FIGURE 1

Tanshinone IIA and curcumol were adopted as quality controls for Taodan granule (TDG). Tanshinone IIA and curcumol are detected in both positive control and TDG samples but neither found in the negative control.


FIGURE 2



FIGURE 2

Taodan granules (TDGs) alleviated back lesions in imiquimod (IMQ)-induced psoriasis-like mice and decreased keratinocyte proliferation. (A) The appearance of back lesions in each group on day 12. (B) The psoriasis area severity index (PASI) score (0–4) with scales, thickness, erythema, and a total score. (C) Representative H&E sections of back lesions on day 12 (× 200) (Left). Representative immunohistochemistry sections of Ki67 and PCNA nuclear staining (brown) of the back skin lesions (200×) (Middle and Right). Quantification of epidermis thickness as well as Ki67+ and PCNA+ cells in back lesions. Scale bar: 100 µm. The data are expressed as mean ± SD. Four skin lesions from in group were included for analysis. #
p < 0.05, ##
p < 0.01, ###
p < 0.001, compared with the control group. *p < 0.05, **p < 0.01, ***p < 0.001, compared with the IMQ group.


FIGURE 3



FIGURE 3

Differentially expressed genes (DEGs) induced after Taodan granule (TDG) treatment. (A) Cluster analysis of DEGs among samples and groups. The color of the heat map indicates the relative gene expression. The deeper red color indicates the higher gene expression, whereas the deeper blue color indicates the lower gene expression (Left). The volcano map suggests the overall DEGs in the imiquimod (IMQ)+TDG group, compared with the IMQ group (Right). (B) Enriched KEGG analysis of up-(Left) and down-(Right) regulated DEGs. (C) Enriched gene ontology analysis of up-(Left) and down-(Right) regulated DEGs.


FIGURE 4



FIGURE 4

Increased gene expression in GlySer-Thr metabolism axis and decreased gene expression in chemokine signaling pathway as well as inflammatory markers after Taodan granule (TDG) treatment. (A) Expression determined by ELISA: CBS, Sardh, GNMT, Pgam2, and Sdsl in Gly-Ser-Thr axis; Vav1, Lyn, Hck, Prkcb, and CXCL13 in chemokine signaling pathway; IL-17a as well as TNF-α protein in lesions. (B) Representative immunohistochemistry sections of NF-κB nuclear staining (brown) of the back skin lesions (200×). Quantification of NF-κB+ cells in back lesions. Scale bar = 100 μm. The data are expressed as the mean ± SD. Four skin lesions in each group were included for analysis. #
p < 0.05, ##
p < 0.01, ###
p < 0.001, compared with the control group. *p < 0.05, **p < 0.01, ***p < 0.001, compared with the imiquimod (IMQ) group.


FIGURE 5



FIGURE 5

Reduced Rac2 and Arhgdib in lesions following Taodan granule (TDG) treatment. (A) Representative images of Rac2 cytoplasm staining (brown) of back lesions from each group (200×). Scale bar = 100 μm. (B) The expression of Arhgdib protein in lesions determined by ELISA. (C) Western blotting of Rac2 and Arhgdib protein in back lesions on day 12. The data are expressed as mean ± SD. Four skin lesions in each group were included for analysis. #
p < 0.05, ##
p < 0.01, ###
p < 0.001, compared with the control group. *p < 0.05, **p < 0.01, ***p < 0.001, compared with the imiquimod (IMQ) group.

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