Title:The Anti-psoriatic Effect of Gallic Acid is Associated with the Suppression
of Keratin 6 and Nrf2
Volume: 21
Issue: 9
Author(s): Jinwei Zhang, Hong Qiu, Xiaojing Cao and Ling Han*
Affiliation:
- College of the Second
Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
Keywords:
Keratin 6 (KRT 6), psoriasis, gallic acid (GA), Nrf2 signaling pathway, skin biopsies, HaCaT cells, CD3.
Abstract:
Background: Psoriasis is recognized as an autoimmune dermatosis, and keratin 6 (KRT 6) is a
hallmark of psoriasis. Gallic acid (GA) is a natural and small molecule with a series of biological activities.
However, the effect of GA on psoriasis has not been clarified.
Aims: This study aimed to investigate the anti-psoriatic activity of GA in psoriasis-like mice and in vitro.
Methods: The transcriptions of the Homo sapiens KRT6 gene, and Mus musculus KRT6 gene, were identified
using a quantitative real-time reverse transcriptase PCR (qRT-PCR) assay. Expressions of KRT 6,
STAT3, pSTAT3, Nrf2, and pNrf2 in HaCaT cells and skin biopsies were determined with a western
blotting assay. The immunofluorescence (IF) assay was used to examine the expression of KRT6,
pSTAT3, and pNrf2 in HaCaT cells. The expression of KRT 6, PCNA, Ki67, and CD3 was evaluated on
the skin of psoriasis-like mice and quantified with histochemical scores (H scores).
Results: GA significantly inhibited KRT 6 gene transcription and expression in psoriasis-like disease both
in vitro and in vivo. It significantly inhibited the expression of keratinocyte proliferation markers (PCNA
and Ki67), suppressed the expression of CD3 (a marker of T cells), and decreased the thickness of the
folded skin, as well as improved the splenomegaly in imiquimod-induced mice similar to psoriasis. Furthermore,
the suppressing effect of GA on KRT 6 was abolished by the continuous activation of Nrf2
rather than STAT3, although GA significantly inhibited Nrf2 and STAT3 activation in IL-17A-induced
HaCaT cells.
Conclusions: KRT 6 acts as a potential target for GA against psoriasis, and the anti-psoriatic effect of GA
could be related to Nrf2 signaling.