milk fat globule epidermal growth factor Ⅷ

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvβ3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy...

OBJECTIVE: Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the function of mesenchymal cells. We characterised the composition and function of ECM in fibrostenosing Crohn's disease (CD) and control tissues. DESIGN: Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, and ECM composition in different tissue phenotypes was explored by proteomics and validated by quantitative PCR (qPCR) and immunohistochemistry...

The direction and magnitude of immune responses are critically affected when dead cells are disposed of. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) promotes the engulfment of apoptotic normal and cancerous cells without inducing inflammation. We have previously reported that a certain proportion of the cancer cells express abundant MFG-E8, and that such expression is associated with the shorter survival of patients with esophageal cancer who had received chemotherapy before surgery. However, the influence of tumor-derived and systemically existing MFG-E8 on antitumor immune responses has not yet been fully investigated...

Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear...

Integrins are cell adhesion receptors that dimerize to mediate cell-cell interactions and regulate processes including proliferation, inflammation, and tissue repair. The role of integrins in regulating insulin signaling is incompletely understood. We have previously shown that binding of the integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) to the αvβ5 integrin promotes termination of insulin receptor signaling in mice. Upon ligation of MFGE8, integrin β5 complexes with the insulin receptor beta (IRβ) in skeletal muscle, resulting in dephosphorylation of IRβ and reduction of insulin-stimulated glucose uptake...

BACKGROUND: Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) has been reported to play an oncogenic role in a variety of tumors. However, its involvement in gastric cancer (GC) development has not been described. METHODS: The cancer genome atlas (TCGA) and the gene expression omnibus database (GEO) databases were used to analyze the expression of MFG-E8 in GC. These findings were further validated using immunohistochemistry (IHC) and western blotting assay (WB)...

Human milk fat globule epidermal growth factor-factor VIII (MFG-E8) functions as a bridging molecule to promote the removal of dying cells by professional phagocytes. E. coli-expressed histidine-tagged recombinant human MFG-E8 (rhMFG-E8) is protective in various disease conditions. However, due to improper recombinant protein glycosylation, misfolding and the possibility of antigenicity, E. coli-expressed histidine-tagged rhMFG-E8 is unsuitable for human therapy. Therefore, we hypothesize that human cell-expressed, tag-free rhMFG-E8 will have suitable structural and functional properties to be developed as a safe and effective novel biologic to treat inflammatory diseases including radiation injury...

In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug-loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG-E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier...

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter injury. Microglia phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white matter. However, milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a microglial phagocytosis-related protein, has not been well studied in hypoperfusion-related cognitive dysfunction. We found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis (BCAS)...

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus that leads to end-stage renal disease. Hyperglycemia triggers apoptosis and kidney damage. Milk fat globule-epidermal growth factor 8 (MFG-E8) and TAM receptor tyrosine kinases, Tyro3, Axl, and Mer, are phagocytic receptors that mediate the clearance of apoptotic cells. This study aimed to identify the role of MFG-E8 and TAM receptors in the development of DN. METHODS: A total of 146 patients with type 2 diabetes mellitus (T2DM), early stage DN, clinical DN and 48 healthy controls were employed to analyze the serum levels of MFG-E8, soluble Tyro3, Axl, Mer, and RAGE by enzyme-linked immunosorbent assay...

Sepsis is a life-threatening inflammatory condition partly orchestrated by the release of various damage-associated molecular patterns (DAMPs) such as extracellular cold-inducible RNA-binding protein (eCIRP). Despite advances in understanding the pathogenic role of eCIRP in inflammatory diseases, novel therapeutic strategies to prevent its excessive inflammatory response are lacking. Milk fat globule-epidermal growth factor-VIII (MFG-E8) is critical for the opsonic clearance of apoptotic cells, but its potential involvement in the removal of eCIRP was previously unknown...

Milk fat globule epidermal growth factor VIII (MFG-E8) and whey protein have emerged as promising bionutrient supplements for enhancing skeletal muscle mass and function. In the present study, aging-related sarcopenia rat model was employed to elucidate the effects of the combined administration of MFG-E8 and whey protein on the catabolism and anabolism of gastrocnemius protein. Combined intervention led to notable enhancements in the anti-oxidative stress status and mitochondrial biogenesis capacity of gastrocnemius muscle fibers in the aging rats, concomitant with a significant inhibition of lipid accumulation...

Human milk adipokines in term babies seem partially determined by maternal factors and affect infant's development. We aimed to describe bioactive peptide concentration in very preterm human milk and associations to maternal characteristics and postnatal growth. Mothers delivering ≤32 weeks of gestation and their infant/s were recruited. At 4 weeks of lactation, an aliquot of 24-h-pooled milk was collected for exclusively breastfeeding dyads. Insulin, leptin, adiponectin, and milk fat globule epidermal growth factor-8 (MFG-E8) were measured by enzyme-linked immunoabsorbent assay in skimmed milk...

BACKGROUND: Milk fat globule-epidermal growth factor 8 (MFG-E8) is expressed in the endometrial epithelium and its expression increases during the implantation process. Due to this knowledge, we aimed to investigate the maternal serum MFG-E8 levels on both healthy pregnant women in the first trimester and pregnant women complicated with missed abortion and threatened abortion in the first trimester. METHODS: This prospective, cross-sectional study was conducted in a tertiary referral hospital, department of obstetrics between July 2020 and February 2021 after ethical committee approval...

The role of integrins in regulating insulin signaling is incompletely understood. We have previously shown that binding of the integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) to the αvβ5 integrin promotes termination of insulin receptor signaling in mice. Upon ligation of MFGE8, β5 complexes with the insulin receptor beta (IRβ) in skeletal muscle resulting in dephosphorylation of IRβ and reduction of insulin-stimulated glucose uptake. Here we investigate the mechanism by which the interaction between β5 and IRβ impacts IRβ phosphorylation status...

Background Human milk fat globule epidermal growth factor-factor VIII (MFG-E8) functions as a bridging molecule to promote the removal of dying cells by professional phagocytes. E. coli-expressed histidine-tagged recombinant human MFG-E8 (rhMFG-E8) is protective in various disease conditions. However, due to improper recombinant protein glycosylation, misfolding and possible antigenicity, E. coliexpressed histidine-tagged rhMFG-E8 is unsuitable for human therapy. Therefore, we hypothesize that human cell-expressed, tag-free rhMFG-E8 can be developed as a safe and effective novel biologic to treat inflammatory diseases such as radiation injury and acute kidney injury (AKI)...

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs...

Mfge8, a secreted glycoprotein, is a key molecule that mediates the phagocytosis of apoptotic cells. Previous research reported that Mfge8 is critical for the proliferation and differentiation of radial glial cells (RGCs) in the dentate gyrus of adult mice. The treatment of Mfge8 is also beneficial for the repair of central nervous system (CNS) injury after cerebral ischemia. This study aimed to investigate whether the expression of mfge8a in zebrafish embryos was associated with the development of CNS and larval behavior...

Medin, a small 50-amino acid peptide, is an internal cleaved product from the second discoidin domain of milk fat globule epidermal growth factor VIII (MFG-E8) protein. Medin has been reported as the most common amylogenic protein in the upper part of the arterial system, including aortic, temporal, and cerebral arterial walls in the elderly. Medin has a high affinity to elastic fibers and is closely associated with arterial degenerative inflammation, elastic fiber fragmentation, calcification, and amyloidosis...

OBJECTIVE: Endometrial cancer (EC) is a common gynecological malignant tumor. CircRNAs play crucial roles in cancer progression and metastasis. However, the biological functions of circRNAs in EC remain largely unknown. METHODS: CircSMAD2, miR-1277-5p, MFGE8 and relative maker protein expression in EC tissues or cell lines were analyzed by quantitative real-time polymerase chain reaction and Western blot. In vitro and in vivo functional assays, including EDU, CCK8, colony formation, transwell, tube formation and tumor xenograft assays, were conduct to explore the effects of circSMAD2 on EC...