We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans.
B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c<sup>+</sup> or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6.
We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway.
B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c<sup>+</sup> or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6.
We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans.
Using gene-gene interaction network analysis, relevant core genes, including MET, UBB, GNAI3, and GNA13, were shown to hold a potential relationship with the development of OA in cartilage.
In order to address these questions, we searched for alterations in PLCB4, GNAI3, and EDN1 in patients with typical Auriculocondylar syndrome (n = 3), Pierre Robin sequence-plus (n = 3), micrognathia with additional craniofacial malformations (n = 4), or non-specific auricular dysplasia (n = 1), which could represent subtypes of Auriculocondylar syndrome.
In this study, we screened the human Gαi3 gene, GNAI3, in DNA samples from 26 patients who had all clinical characteristics of OA but in whom a specific mutation in the OA1 gene had not been found, and in 6 normal control individuals.
We found that ACS-associated mutations in GNAI3 produce dominant-negative Gα(i3) mutant proteins that couple to ET(A)R but cannot bind and hydrolyze guanosine triphosphate, resulting in the prevention of endothelin-mediated activation of Gα(q/11) and PLC.
Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing.