Primary murine hepatocytes were transfected with siRNA targeting Caveolin-1 directly after attachment (o/n). Next day, cells were treated with TGF-beta for 48 h. Experiment was performed in triplicate using primary cells from 3 donor mice.
Caveolin-1 Impacts on TGF-β Regulation of Metabolic Gene Signatures in Hepatocytes.
Treatment
View SamplesmRNA expression was compared between wild type and hepatocyte-specific caveolin-1 knockout livers in healthy and non-alcoholic fatty liver disease (NAFLD) mice
Hepatocyte caveolin-1 modulates metabolic gene profiles and functions in non-alcoholic fatty liver disease.
Sex
View SamplesRegulatory T cells (Treg) are common in the tumor microenvironment in both human pancreatic cancer and in genetically engineered mouse models of the disease. Previous studies in orthotopic syngeneic models of pancreatic cancer -recapitulated in our own data- indicated that Treg depletion results CD8+ T cell-mediated tumor regression. In human patients and in mouse models, regulatory T cells accumulate during the onset of Pancreatic Intraepithelial Neoplasia (PanIN), the earliest steps of carcinogenesis. We thus generated a genetic model to investigate the role of regulatory T cells during the onset of pancreatic carcinogenesis. Unexpectedly, depletion of Tregs during early stages of carcinogenesis led to accelerated tumor progression. Overall design: We are using KC;Foxp3DTR mice generated by crossing KC (Ptf1a-Cre;LSL-KrasG12D) with Foxp3DTR (B6.129(Cg)-Foxp3tm3(DTR/GFP)Ayr/J, Jackson Laboratory). We depleted Foxp3-expressing Tregs by Diphtheria Toxin (DT) injection to determine the requirement of Tregs during oncogenic Kras induced Pancreatic Intraepithelial Neoplasia (PanIN) formation and maintenance. To investigate the mechanisms underlying the tumor-promoting effect of Treg depletion in KC; Foxp3DTR mice we performed RNA sequencing (RNAseq) for myeloid cells (DAPI-EpCAM-CD45+CD11b+) flow-sorted from KC and KC; Foxp3DTR pancreata.
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis.
Subject
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