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.
Bibliographical noteFunding Information:
agencies: This project was supported by grant 16GRNT31210025 from the American Heart Association, by grant 1-18-IBS-287 from the American Diabetes Association, and by the Allen Foundation to XC.We thank Dr. Martin Matzuk (Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas) for kindly providing PTX3 KO mice for the project.
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't