| First Author | Li X | Year | 2023 |
| Journal | Cell Commun Signal | Volume | 21 |
| Issue | 1 | Pages | 24 |
| PubMed ID | 36717921 | Mgi Jnum | J:332965 |
| Mgi Id | MGI:7431552 | Doi | 10.1186/s12964-022-01024-w |
| Citation | Li X, et al. (2023) Semaphorin 7A interacts with nuclear factor NF-kappa-B p105 via integrin beta1 and mediates inflammation. Cell Commun Signal 21(1):24 |
| abstractText | Semaphorin7a (SEMA7A), a membrane-anchored member of the semaphorin protein family, could be involved in a diverse range of immune responses via its receptor integrin beta1. Recently, we reported that the SEMA7A(R148W) mutation (a gain-of-function mutation, Sema7a(R145W) in mice) is a risk factor for progressive familial intrahepatic cholestasis and nonalcoholic fatty liver disease via upregulated membrane localization. In this study, we demonstrated that integrin beta1 is a membrane receptor for nuclear factor NF-kappa-B p105 (NF-kappaB p105) and a critical mediator of inflammation. Integrin beta1 could interact with the C-terminal domain of NF-kappaB p105 to promote p50 generation and stimulate the NF-kappaB p50/p65 signalling pathway, upregulate TNF-alpha and IL-1beta levels, and subsequently render hepatocytes more susceptible to inflammation. The induction of integrin beta1 depends on elevated Sema7a membrane localization. Moreover, we revealed elevated levels of Sema7a(WT) (SEMA7A(WT)) in hepatocellular carcinoma (HCC) patients and an HCC mouse model. In line with our findings, the NF-kappaB p50/p65 pathway could also be activated by high Sema7a expression and repressed by integrin beta1 silencing. In conclusion, our findings suggest that the Sema7a(R145W) (SEMA7A(R148W)) mutation and high Sema7a(WT) (SEMA7A(WT)) expression both activate the NF-kappaB p50/p65 pathway via integrin beta1 and play a crucial role in inflammatory responses. Video Abstract. |
