Lysine Methyltransferases SMYD2 and SMYD3: Emerging Targets in Kidney Diseases.

BACKGROUND

The SET and MYND domain-containing (SMYD) protein family is a group of lysine methyltransferases with SET and MYND domains and plays a critical role in regulating gene expression through the methylation of histone and non-histone proteins.

SUMMARY: Studies have linked mutations or overexpression of SMYD2 and SMYD3 to various cancers, including renal carcinoma. Recent research also demonstrates that the expression levels and activity of SMYD2 and SMYD3 are increased in animal models of renal diseases such as autosomal dominant polycystic kidney disease, renal fibrosis, and diabetic nephropathy. Inhibiting either SMYD2 or SMYD3 pharmacologically or genetically can effectively suppress renal tumorigenesis and cystic formation while improving outcomes in renal fibrosis and diabetic nephropathy. Additionally, SMYD2 and SMYD3 are involved in the pathogenesis of acute kidney injury.

KEY MESSAGES: This review summarizes the roles of these two lysine methyltransferases in renal diseases, highlights their mechanisms, and emphasizes their potential as therapeutic targets for kidney disorders.