The first link between ADAMTS-13 and apoptosis in type 1 diabetic liver injury.

Abstract

Type 1 diabetes mellitus (T1DM) is associated with oxidative stress and inflammation in the liver, which contribute to hepatocellular damage. However, the molecular mechanisms driving this process remain poorly understood. ADAMTS-13, a metalloprotease involved in vascular homeostasis, has been implicated in tissue remodeling and apoptosis. This study explores the potential link between ADAMTS-13 and apoptosis in T1DM-induced liver injury. Diabetes was induced in Wistar albino rats via streptozotocin (STZ) injection, and liver tissues were examined using immunohistochemical staining for ADAMTS-13 and apoptotic markers, including caspase-3, caspase-8, caspase-9, and TNFR1. Expression levels were compared between diabetic and control groups to assess correlations with apoptotic pathways. ADAMTS-13 expression was significantly elevated in the diabetic group. Apoptotic markers also showed a significant increase (p < 0.05). Notably, caspase-9 expression was more prominent in hepatocytes, indicating activation of the intrinsic apoptotic pathway, while caspase-8 and TNFR1 were predominantly expressed in sinusoidal and vascular endothelial cells, suggesting involvement of the extrinsic pathway. This study is the first to demonstrate a link between ADAMTS-13 expression and apoptosis in T1DM-related liver injury. These findings suggest that ADAMTS-13 may play a role in modulating apoptotic responses, although its exact function remains to be clarified. Further mechanistic studies are warranted to determine whether ADAMTS-13 directly influences apoptosis or represents an adaptive response to hepatic stress. Additionally, the results highlight the potential of ADAMTS-13 as a biomarker for diabetes-associated liver dysfunction.