The Wnt/β-catenin signaling pathway is concerned within the production of extracellular matrix (ECM) by mesangial cells (MCs). Recent research by us and others demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have protecting results in opposition to diabetic nephropathy. The function of this examine was to analyze whether or not the Wnt/β-catenin signaling in MCs contributed to GLP-1RA-induced inhibition of ECM accumulation and mitigation of glomerular injury in diabetic nephropathy. In cultured human mesangial cells (HMCs), liraglutide (a GLP-1RA) therapy considerably diminished excessive glucose (HG)-stimulated production of fibronectin (FN), collagen IV (Col IV) and α-smooth muscle actin (α-SMA) and the liraglutide results had been considerably attenuated by XAV-939, a selective inhibitor of the Wnt/β-catenin signaling.
Furthermore, HG therapy considerably decreased the protein abundance of Wnt4, Wnt5a, phospho-glycogen synthase kinase-3β and β-catenin. These HG results on the Wnt/β-catenin signaling proteins had been considerably blunted by liraglutide therapy. For in vivo research, we administered liraglutide (200μg/kg/12h) by subcutaneous injection to streptozocin-induced sort 1 diabetic rats for eight weeks. Administration of liraglutide considerably improved elevated blood urine nitrogen, serum creatinine, and urinary albumin excretion charge, and alleviated renal hypertrophy, mesangial growth, and glomerular fibrosis in sort 1 diabetic rats whereas blood glucose stage and physique weight didn’t have vital adjustments.
Consistent with the in vitro research, liraglutide therapy considerably diminished the diabetes-induced will increase in glomerular FN, Col IV and α-SMA, and decreases in glomerular Wnt/β-catenin signaling proteins. These outcomes recommend that liraglutide alleviated glomerular ECM accumulation and renal injury in diabetic nephropathy by enhancing the Wnt/β-catenin signaling.
Transmembrane protein 88 exerts a tumor-inhibitory position in thyroid most cancers via restriction of Wnt/β-catenin signaling
Transmembrane protein 88 (TMEM88) has emerged as a newly found cancer-related protein that acts as a cancer-promoting or cancer-inhibiting regulator in a number of tumor varieties. However, the precise position of TMEM88 in thyroid most cancers is undetermined. The present examine was designed to find out the expression, operate, and potential underlying mechanism of TMEM88 in thyroid most cancers. Our knowledge demonstrated low TMEM88 expression in thyroid most cancers tissues. Decreased TMEM88 expression was additionally present in a number of thyroid most cancers cell traces, and restoration of TMEM88 markedly suppressed the proliferation, colony formation, and invasive potential of thyroid most cancers cells.
On the opposite, TMEM88 depletion considerably accelerated the proliferation, colony formation, and invasion of thyroid most cancers cells. Further experiments documented that TMEM88 overexpression markedly decreased the expression of the energetic type of β-catenin and inhibited the expression of Wnt/β-catenin signaling targets genes, equivalent to c-myc and cyclin D1. Notably, reactivation of Wnt/β-catenin signaling by transfecting a vector that expressed constitutively energetic β-catenin partially reversed the TMEM88-mediated suppressive impact on thyroid most cancers cell proliferation and invasion. In addition, TMEM88 upregulation markedly retarded the tumor development of thyroid most cancers cells in vivo utilizing xenograft fashions related to downregulation of energetic β-catenin expression.
Taken collectively, our findings demonstrated that TMEM88 overexpression impeded the proliferation and invasion of thyroid most cancers cells via downregulation of Wnt/β-catenin signaling. These knowledge point out a possible tumor-suppressive operate of TMEM88 in thyroid most cancers. Our examine highlights a key position for TMEM88 in regulating Wnt/β-catenin signaling through the development of thyroid most cancers and means that TMEM88 is a lovely anticancer goal for thyroid most cancers.
Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/β-catenin signaling
Spindle and kinetochore-associated protein 2 facilitates the proliferation and invasion of hepatocellular carcinoma through the regulation of Wnt/β-catenin signaling
Recent research have proven that spindle and kinetochore-associated protein 2 (SKA2) is dysregulated in a number of tumors and acts as a key regulator of tumor development. However, whether or not SKA2 performs a job in hepatocellular carcinoma (HCC) has not been totally elucidated. The function of this examine was to discover the expression, operate and underlying molecular mechanism of SKA2 in HCC. We discovered that SKA2 was extremely expressed in HCC tissues and cell traces. Knockdown of SKA2 precipitated marked reductions within the proliferative, colony-forming and invasive capacities of HCC cells, whereas SKA2 overexpression had reverse results. Further experiments revealed that overexpression of SKA2 enhanced expression ranges of phosphorylated glycogen synthase kinase-3β (GSK-3β) and energetic β-catenin in HCC cells.
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Moreover, SKA3 overexpression enhanced transcriptional exercise mediated by Wnt/β-catenin signaling. Knockdown of SKA3 downregulated the activation of Wnt/β-catenin signaling, and the impact was considerably reversed by the inhibition of GSK-3β. Notably, inhibition of Wnt/β-catenin signaling markedly abrogated SKA2-mediated promotion impact on HCC proliferation and invasion. In addition, knockdown of SKA2 impeded tumor formation and development in HCC cells in a nude mouse in vivo mannequin. Overall, these findings point out that SKA2 accelerates the development of HCC via the upregulation of Wnt/β-catenin signaling. Our examine highlights a possible position of SKA2 in HCC development and suggests it as a attainable goal for HCC therapy.
