The Role Of Trim65 In Vascular Calcification And Its Mechanism

TRIM65,a member of the TRIM family, is widely expressed in various tissues, but its role in vascular function remains unclear. This study investigates the role of TRIM65 in vascular calcification using an in vitro mouse VSMC calcification model. Wei S, Huang X, Zhu Q, Chen T, Zhang Y, Tian J, Pan T, Zhang L, Xie T, Zhang Q, Kuang X, Lei E, Li Y. TRIM65 deficiency alleviates renal fibrosis through NUDT21-mediated alternative polyadenylation. Cell Death Differ. 2024,31(11):1422-1438. VSMC calcification was induced in vitro for 0,3,and 5 days. Western blot and q-PCR were used to assess the expression of osteopontin(OPN),Runx2,and TRIM65.Calcium nodules were visualized by alizarin red S staining, and calcium content was measured using the o-cresolphthalein complexone method. The role of TRIM65 was further explored through knockdown and overexpression experiments in VSMCs, with GST-pulldown and co-immunoprecipitation(co-IP)used to identify potential molecular interactions. TRIM65 expression significantly increased during VSMC calcification. Overexpression of TRIM65 exacerbated calcification and cell migration/proliferation, while knockdown had the opposite effect. Mechanistic studies revealed that TRIM65 interacts with catalase(CAT),leading to its degradation and subsequent effects on calcification. TRIM65 plays a crucial role in VSMC calcification by regulating catalase activity. Targeting the TRIM65-CAT axis may offer a potential therapeutic strategy for vascular calcification-related diseases. Future research should focus on in vivo validation and further elucidation of the underlying molecular mechanisms.