| First Author | Chen Y | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 10 | Pages | 2712-2723 |
| PubMed ID | 31597705 | Mgi Jnum | J:282055 |
| Mgi Id | MGI:6370216 | Doi | 10.4049/jimmunol.1900212 |
| Citation | Chen Y, et al. (2019) Gasdermin D Drives the Nonexosomal Secretion of Galectin-3, an Insulin Signal Antagonist. J Immunol 203(10):2712-2723 |
| abstractText | The inflammasomes play critical roles in numerous pathological conditions largely through IL-1beta and/or IL-18. However, additional effectors have been implied from multiple studies. In this study, through two independent mass spectrometry-based secretome screening approaches, we identified galectin-3 as an effector protein of the NLRP3 inflammasome. Although the activation of AIM2 or NLRC4 inflammasome also led to galectin-3 secretion, only the NLRP3 inflammasome controlled the serum galectin-3 level under physiological condition. Mechanistically, active gasdermin D drove the nonexosomal secretion of galectin-3 through the plasma membrane pores. In vivo, high-fat diet-fed Nlrp3(-/-) mice exhibited decreased circulating galectin-3 compared with wild-type animals. Of note, the improved insulin sensitivity in such Nlrp3(-/-) mice was aggravated by infusion of recombinant galectin-3. Moreover, galectin-3 was essential for insulin resistance induction in mice harboring the hyperactive Nlrp3(A350V) allele. Thus, the inflammasome-galectin-3 axis has been demonstrated as a promising target to intervene inflammasome and/or galectin-3 related diseases. |
