Background: Wnt/β-catenin signaling is involved in glucose and lipid metabolism, but the mechanism is not clear yet.
Aim: The objective is to study mechanisms of Wnt/β-catenin signaling on regulating hepatocytes metabolism.
Methods: Real-time qPCR, Western blot, and Oil-red O staining methods were used.
Results: The Wnt/β-catenin signaling was activated in hepatocytes by CP21R7, and the level of phosphorylated IRS-1 (Ser307) and TRB3 were significantly increased, while the levels of phosphorylated IRS-1 (Tyr612) and phosphorylated Akt were decreased. Moreover, the expression of FGF21, FAS, SCD1, PPARγ and ADRP was significantly increased. The expression of ATF4, ATF5, eIF2α, GRP78, CHOP and phosphorylated level of PERK were also increased. The expression of FGF21 and TRB3 was significantly down-regulated, and the lipid droplets were notably reduced after the ER stress was inhibited by TUDCA. The expression of FGF21 was significantly decreased when the IRE1 pathway of the UPR was inhibited by STF-083010.
Conclusions: Activation of Wnt/β-catenin signaling pathway could cause insulin resistance and lipogenesis in hepatocytes via regulation of the IRE1 pathway of the ER stress and UPR, providing new targets for the treatment of metabolic disorders.
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http://dx.doi.org/10.1016/j.bbrc.2020.03.147 | DOI Listing |
Mol Biotechnol
March 2025
The Third Clinical Medicine College, Ningxia Medical University (People's Hospital of Ningxia Hui Autonomous Region), Yinchuan, 750002, China.
The activity of Wnt inhibitory factor 1 (WIF1) is reduced upon promoter methylation and is involved in cartilage degradation in osteoarthritis. This study aims to investigate the mechanism by which WIF1 methylation is involved in chondrocyte damage in ankylosing spondylitis (AS). A model of chondrocyte inflammatory injury in AS was constructed by stimulation with interleukin (IL)-17.
View Article and Find Full Text PDFAging Dis
March 2025
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, 24252, Gangwon-do, Korea.
Age-related alterations in the skeletal system are linked to decreased bone mass, a reduction in bone strength and density, and an increased risk of fractures and osteoporosis. Therapeutics are desired to stimulate bone regeneration and restore imbalance in the bone remodeling process. Quercetin (Qu), a naturally occurring flavonoid, induces osteogenesis; however, its solubility, stability, and bioavailability limit its therapeutic use.
View Article and Find Full Text PDFMed Res Rev
March 2025
Biochemistry and Molecular Biology, Primeasia University, Banani, Dhaka, Bangladesh.
The development of standard drugs for some unusual cancers, including estrogen-nonresponsive breast cancer, is somewhat difficult within a very short time. So, considering the current situation, phytoestrogen may be a potential candidate for unraveling chemotherapeutics agents. The reason for this review article is to manifest overall information regarding the effects of phytoestrogen on triple-negative breast cancer (TNBC), along with its related cellular and molecular pathways in different TNBC models.
View Article and Find Full Text PDFCells
March 2025
Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil.
Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells-either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)-modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9.
View Article and Find Full Text PDFiScience
March 2025
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
The specific roles of nonsense-mediated mRNA decay (NMD), a translation-dependent RNA quality control mechanism that degrades mRNAs containing premature termination codons (PTCs), in mammalian craniofacial development have remained unclear. Here, we show that knockout of the essential NMD factor in mouse craniofacial neural crest cells leads to hypoplastic mandibles, subsequently inducing tongue mispositioning and cleft palate formation. Furthermore, loss triggers massive cell apoptosis and disrupts cell differentiation, accompanied by widespread alterations in alternative splicing and a surge in PTC-containing mRNA levels.
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