Page 58 - JCBP-2-3

Journal of Clinical and
Basic Psychosomatics Proteomic analysis of mind-body psychotherapy in psoriasis

healing. Downregulation of these proteins in the plasma-
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derived exosome may also indicate the deterioration of
skin organization in psoriasis. Upregulation of COIA1
and CAP1 may alter skin organization in psoriasis because
CAP1 was reported to inhibit endothelial cell proliferation
and angiogenesis. A study revealed that CAP1 controlled
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the actin cytoskeleton and its interactions with various
actin-binding proteins in cellular processes. 38
These data were fed into KEGG pathway analysis to
decipher the functional and pathological roles of these
changes. KEGG pathway analysis identified two pathways
involved in psoriasis: ribosome signaling pathway (https://
www.kegg.jp/dbget-bin/www_bget?map03010), and
apelin signaling pathway (https://www.kegg.jp/dbget-
bin/www_bget?map04371). The peptidase inhibitor-3K
Figure 4. Significant differences in serum elafin between HCs and
psoriasis patients and the changes in elafin level after MMIP. Statistical (PI3K)/Akt pathway acts downstream of the apelin pathway
difference in elafin level before and after therapy was analyzed using and regulates synthesis of osteopontin (OPN), which is
Wilcoxon matched-pair signed rank test, wheras statistical difference known to be enhanced in psoriasis lesions and decrease
in elafin level between HCs and psoriasis patients was analyzed using after anti-TNF therapy. OPN is a multifunctional protein
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Mann–Whitney U-test (** P < 0.01; ****P < 0.0001).
Abbreviations: MMIP: Mongolian mind-body interactive psychotherapy; synthesized by various immune-inflammatory cells,
HCs: Healthy controls. involved in diabetes, cardiovascular disease, and kidney
disease, and often associated with psoriasis. This finding
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is the first observation made with exosome proteomics
analysis that the apelin signaling pathway is involved
in psoriasis, further indicating that various metabolic
pathways are altered in psoriasis.
Interestingly, PAI1 and ACTA2, which are reportedly
involved in psoriasis, showed opposing alteration. 41,42 PPI
analysis shed light on interesting PPI in psoriasis, showing
that the ACTA2, one of six different actin isoforms, is
involved in the contractile apparatus of smooth muscle,
ACTA2 upregulation is associated with various RS proteins
and COLA1, and COLA1 is related to CELR2. These three
proteins were upregulated in patients with psoriasis, and
Figure 5. Venn diagram showing overlapping of differentially expressed the interaction of actin and cadherins was identified
proteins in plasma exosome between two study groups (Disease vs. in the keratinocyte cell line. Their upregulation was
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Health; Therapy vs. Disease).
associated with a decrease of PKP1, a regulator of WNT
signaling, and also known to play a prominent role in the
4.1. Comparative analysis of exosomal proteome desmosomes of keratinocytes in psoriasis. It is necessary
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between psoriasis patients and HCs to obtain tissue and plasma simultaneously from the same
Comparing the exosomal proteome psoriasis patients and patient and conduct a comparative study to understand
HC, we found that the levels of 41 proteins were altered in its pathological roles. Moreover, the interaction of ELAF
psoriasis patients. Among the four proteins that participate (a potent inhibitor specific for elastase and proteinase)
in skin function, KRT17 and PKP1 were downregulated, and CO3 (complement 3) was identified. It is speculated
while COIA1 and CAP1 were upregulated in patients with that there is a circuit involving an increase in CO3 and an
psoriasis (Table 2 and Figure 2B). KRT17 is essential for increase in elastase (which cleaves CO3), a concomitant
lipid metabolism in keratinocytes and is beneficial for increase in ELAF (which inhibits elastases), and an
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the homeostasis of the epidermal permeability barrier. elevation of ELAF in patients with psoriasis. Thus, we
Another investigation revealed that PKP1 plays a key role and others confirmed an elevation of ELAF in PS and the
in desmosome and tight junction function, and supports interaction of these three molecules may be important in
its role in growth control, which is essential for wound the pathogenesis of PS.

Volume 2 Issue 3 (2024) 10 doi: 10.36922/jcbp.2381