Pentraxin 3 deficiency ameliorates streptozotocin-induced pancreatic toxicity via regulating ER stress and 13-cell apoptosis

Abstract

The long pentraxin 3 (PTX3), a marker of inflammation, has been associated with cardiovascular disease, obesity, and metabolic syndrome. Recently, elevated serum PTX3 levels have been linked to type 2 diabetes in obese patients with nonalcoholic fatty liver disease. Diabetes mellitus is a metabolic syndrome characterized by hyperglycemia resulting from insufficient insulin secretion or action. However, the precise role of PTX3 in hyperglycemia remains unclear. This study aimed to investigate the physiological roles of PTX3 in vivo. The deformation of pancreatic islets was mitigated in PTX3deficient mice treated with streptozotocin (STZ) compared to control C57BL/6J mice. In addition, PTX3 deficiency prevented STZ-induced unfolded protein responses and pancreatic 13-cell death. Immunoblotting data revealed significant inhibition of inositol-requiring protein1 alpha and C/EBP homologous protein (CHOP) protein expression in PTX3 KO mice administered tunicamycin which is a chemical endoplasmic reticulum stress inducer. Similarly, tunicamycin-induced Grp78, Grp94, ATF6, and CHOP mRNA levels were reduced in PTX3 KO mice. Moreover, recombinant PTX3-induced CHOP expression and 13-cell apoptosis in primary mouse islets. These findings suggest that PTX3 plays a critical role in STZinduced deformation of pancreatic islets via regulating endoplasmic reticulum stress and 13-cell apoptosis. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of Korean Society for Molecular and Cellular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).