Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene Expression in d5 wound-edge tissues of MFG-E8 WT and MFG-E8 KO mice

ABSTRACT: Gene Expression in d5 wound-edge tissues of MFG-E8 WT and MFG-E8 KO mice Affymetrix GeneChipÂ® Mouse Genome 430 array was used to study the gene expression in d5 wound-edge tissues of MFG-E8 WT and MFG-E8 KO mice Gene Expression in d5 wound-edge tissues of MFG-E8 WT and MFG-E8 KO mice

ORGANISM(S): Mus musculus

SUBMITTER: Sashwati Roy

PROVIDER: E-GEOD-73229 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.

Das Amitava A Ghatak Subhadip S Sinha Mithun M Chaffee Scott S Ahmed Noha S NS Ahmed Noha S NS Parinandi Narasimham L NL Wohleb Eric S ES Sheridan John F JF Sen Chandan K CK Roy Sashwati S

Journal of immunology (Baltimore, Md. : 1950) 20160518 12

Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates ...[more]

PMID: 27194784

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Project description:The mammary gland is a unique apocrine gland made up of a branching network of ducts that end in alveoli. It is an ideal system to study the molecular mechanisms associated with cell proliferation, differentiation, and oncogenesis. MFG-E8, also known as Lactadherin, is a vital glycoprotein related to the milk fat globule membrane and initially identified to get secreted in bovine milk. Our previous report suggests that a high level of MFG-E8 is indicative of high milk yield in dairy animals. Here, we showed that MFGE-E8 controls the cell growth and morphology of epithelial cells through a network of regulatory transcription factors. To understand the comprehensive action, we downregulated its expression in MECs by MFG-E8 specific shRNA. We generated a knockdown proteome profile of differentially expressed proteins through a quantitative iTRAQ experiment on a high-resolution mass spectrometer (Q-TOF). The downregulation of MFG-E8 resulted in reduced phagocytosis and cell migration ability, whereas it also leads to more lifespan to knockdown vis-a-vis healthy cells, which is confirmed through BrdU, MTT, Neutral red, and Caspase 3/7. The bioinformatics analysis revealed that MFG-E8 knockdown perturbs a large number of intracellular signaling, eventually leading to cessation in cell growth. Based on the Weighted Gene Coexpression Network Analysis and directed network, we found that MFG-E8 is activated by CX3CL1, TP63, and CSF2 and leads to the activation of SOCS3 and CCL2 for the regulation of cell proliferation. We further proved that the depletion of MFG-E8 resulted in activated cytoskeletal remodeling by MFG-E8 knockdown, which results in the activation of three independent pathways ZP4/JAK-STAT5, DOCK1/STAT3, and PIP3/AKT/mTOR. Overall, this study suggests that MFG-E8 expression in mammary epithelial cells is an indication of intracellular deterioration in cell health. To date, to the best of our knowledge, this is the first study that explores the downstream targets of MFG-E8 involved in the regulation of mammary epithelial cell health.

Dataset Information

Gene Expression in d5 wound-edge tissues of MFG-E8 WT and MFG-E8 KO mice

Publications

Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.

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