Loss of Galectin-3 in the epidermis exacerbates psoriasis pathogenesis via inhibiting autophagy

Abstract

Aims

Galectin-3 (Gal3) is linked to psoriasis pathophysiology, however, the detailed mechanism of Gal3 involved in this course still needs further addressing. This study aimed to elucidate the role of Gal3 in psoriasis.

Materials and methods

Imiquimod (IMQ)-induced psoriasis model in wild-type (WT) as well as Gal3 knockout (Gal3^−/−) mice were established to investigate the impact of Gal3 expression on the development of psoriasis. Autophagy markers LC3 and P62 (SQSTM1) were detected. In vitro, HaCaT cells with Gal3 knockdown were established to detect the effect on the autophagic flux. Then the Sirt1 agonist SRT1720 was used to demonstrate whether Gal3 affects autophagy via Sirt1. The regulation of Sirt1 by Gal3 was demonstrated through half-life experiments.

Key findings

Gal3 was significantly reduced in the epidermis in IMQ-induced psoriasis model. The skin inflammation in Gal3^−/− mice more severe than that in WT controls. A deficiency of Gal3 not only reduced the autophagy in psoriatic lesions of the mice model but also effectively inhibited autophagy in a cultured HaCaT cell model. Gal3 was demonstrated to be involved in the assembly of autophagosomes by regulating autophagic flux. In Gal3-depleted mouse skin and HaCaT cells, Sirt1 was downregulated, and SRT1720 could compensate for the impaired autophagy caused by Gal3 deficiency. Gal3 may be involved in the regulation of Sirt1 protein stability.

Significance

Gal3 loss exacerbates psoriasis by impairing the autophagic process. These findings position Gal3 as a key protective factor against psoriasis, providing new insights into its role in the pathogenesis of this disease.