| First Author | An Y | Year | 2024 |
| Journal | Int J Biol Sci | Volume | 20 |
| Issue | 3 | Pages | 1004-1023 |
| PubMed ID | 38250155 | Mgi Jnum | J:359894 |
| Mgi Id | MGI:7578048 | Doi | 10.7150/ijbs.87057 |
| Citation | An Y, et al. (2024) Inactivation of MST1/2 Controls Macrophage Polarization to Affect Macrophage-Related Disease via YAP and Non-YAP Mechanisms. Int J Biol Sci 20(3):1004-1023 |
| abstractText | Macrophage polarization is a critical process that regulates in inflammation, pathogen defense, and tissue repair. Here we demonstrate that MST1/2, a core kinase of Hippo pathway and a recently identified regulator of inflammation, plays a significant role in promoting M2 polarization. We provide evidence that inhibition of MST1/2, achieved through either gene-knockout or pharmacological treatment, leads to increased M1 polarization in a YAP-dependent manner, resulting in the development of M1-associated inflammatory disorders. Moreover, MST1/2 inhibition also leads to a substantial reduction in M2 polarization, but this occurs through the STAT6 and MEK/ERK signaling. The STAT6 is independent of YAP, but MEK/ERK is dependent of YAP. Consistent with these observations, both MST1/2-conditional knockout mice and wild-type mice treated with XMU-MP-1, a chemical inhibitor of MST1/2, exhibited reduced M2-related renal fibrosis, while simultaneously displaying enhanced LPS-mediated inflammation and improved clearance of MCR3-modified gram-negative bacteria. These findings uncover a novel role of MST1/2 in regulating macrophage polarization and establish it as a potential therapeutic target for the treatment of macrophage-related fibrotic diseases. |
