Pentraxin 3 Regulates miR-21 Expression and Secretion in Brown Adipocytes During Lipopolysaccharide-Induced Inflammation

Objective: This study investigates the role of pentraxin 3 (PTX3) in the regulation of inflammatory homeostasis involving anti-inflammatory miR-21 during lipopolysaccharide (LPS) stimulation in adipocytes. Methods: Using PTX3 knockout (PTX3 KO) mouse and primary stromal vascular cell models, this study determined the effect of PTX3 deficiency on the expression and secretion of miR-21 in brown adipose tissue (BAT) and brown adipocytes as well as the rescue effect of recombinant PTX3 on miR-21 during LPS-induced inflammation. Results: Among three fat depots, BAT was the major tissue and fully differentiated brown adipocytes were the major cells that expressed miRNA-processing enzymes and produced miRNA. Moreover, brown adipocytes, but not stromal vascular cells, were the LPS-responsive cells in miR-21 production. PTX3 deficiency attenuated LPS-stimulated upregulation of miR-21 in sera and BAT. In wild-type brown adipocytes, LPS stimulation significantly upregulated cellular miR-21. Interestingly, this stimulatory effect of LPS was attenuated, and cellular and secreted miR-21 levels were reduced in PTX3 KO cells upon LPS stimulation. Treatment of recombinant PTX3 reversed the cellular and secreted levels of miR-21 and attenuated an LPS-stimulated increase in the expression of Tnf-α and Mcp1 genes in PTX3 KO adipocytes. Conclusions: PTX3 plays an anti-inflammatory role, in part through regulating miR-21 expression and secretion.