Genome-wide DNA methylation regulated by AHCY through SAM / SAH axis promotes psoriasis pathogenesis

Psoriasis is a chronic inflammatory skin disease that affects a significant proportion of the global population. The involvement of S-adenosine homocysteine hydrolase (AHCY) in psoriasis and its impact on DNA methylation have not been extensively studied.

This study aimed to investigate the role of AHCY and its impact on DNA methylation in psoriasis pathogenesis.

In the present study, we investigated the expression of AHCY in psoriatic lesions and assessed its association with the severity of the disease. Moreover, knockdown experiments were conducted to elucidate the impact of AHCY on psoriatic symptoms, keratinocyte proliferation, and aberrant differentiation. Furthermore, alterations in DNA methylation patterns resulting from AHCY knockdown were analyzed.

Our findings revealed that AHCY was upregulated in psoriatic lesions and exhibited a positive correlation with disease severity. Knockdown of AHCY alleviated psoriatic symptoms, inhibited keratinocyte proliferation, and prevented abnormal differentiation. Moreover, AHCY knockdown led to reduced levels of DNA methylation and alterations in methylation patterns. Notably, differential methylation was observed at specific gene loci associated with psoriasis-related inflammation.

This study highlights the potential role of AHCY in psoriasis development through its influence on DNA methylation. The findings underscore the complex interaction among AHCY, epigenetic modifications, and inflammation in the pathogenesis of psoriasis. Consequently, AHCY may serve as a promising therapeutic target for psoriasis treatment.