| First Author | Liu Y | Year | 2019 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 316 |
| Issue | 2 | Pages | E260-E267 |
| PubMed ID | 30532990 | Mgi Jnum | J:274301 |
| Mgi Id | MGI:6283122 | Doi | 10.1152/ajpendo.00387.2018 |
| Citation | Liu Y, et al. (2019) Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice. Am J Physiol Endocrinol Metab 316(2):E260-E267 |
| abstractText | Plasminogen activator inhibitor-1 (PAI-1) is increasingly recognized as a mediator in extracellular matrix (ECM) accumulation in diabetic nephropathy. Previous studies have implicated PAI-1 in adipose tissue (AT) expansion, while also contributing to insulin resistance. As inflammation is also known to occur in perirenal AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model, PAI-1 contributes to macrophage-mediated inflammation and diabetic nephropathy. The HFD mice showed increased expression of PAI-1 in perirenal fat and also displayed increased fat weight and macrophage numbers. We found that the macrophage polarization, proinflammatory macrophage-M1-phenotype, including CD11c, IL-6, and monocyte chemoattractant protein-1, were increased by an HFD and decreased by either the genetic depletion of PAI-1 or treatment with the PAI-1 inhibitor, PAI-039. Similarly, an enhanced anti-inflammatory M2-phenotype, including CD206 and IL-10, was accompanied by either the genetic deletion of PAI-1 or PAI-039 treatment. Furthermore, the inhibition of PAI-1 reduced HFD-induced renal histological lesions and abated profibrotic/extracellular-matrix protein. Collectively, our findings provide support that PAI-1 contributes to the development of inflammation in perirenal fat and correlates with the development of diabetic nephropathy in HFD-induced obesity. |
