RNA-seq analsis of siRNA knockdown of cadherin-11 (CDH11) gene in human intestinal myofibroblasts (HIMFs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE228619 | GEO | 2024/03/01
REPOSITORIES: GEO
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Project description:RNA-seq analsis of siRNA knockdown of cadherin-11 (CDH11) gene in human intestinal myofibroblasts (HIMFs)
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Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant accumulation of collagen-secreting myofibroblasts. Development of effective therapies is limited due to incomplete understanding of molecular mechanisms regulating myofibroblast expansion. FOXF1 transcription factor is expressed in resident lung fibroblasts, but its role in lung fibrosis remains unknown due to the lack of genetic mouse models. Through comprehensive analysis of human IPF genomics data, lung biopsies and transgenic mice with fibroblast-specific inactivation of FOXF1, the present study shows that FOXF1 inhibits pulmonary fibrosis. FOXF1 deletion increases myofibroblast invasion, collagen secretion, and promotes a switch from of N-cadherin (CDH2) to Cadherin-11 (CDH11), which is critical step in acquisition of pro-fibrotic phenotype. FOXF1 directly binds to Cdh2 and Cdh11 promoters and differentially regulates transcription of these genes. Re-expression of CDH2 or inhibition of CDH11 in FOXF1-deficient cells reduces myofibroblast invasion in vitro. FOXF1 inhibits pulmonary fibrosis by regulating a switch from CDH2 to CDH11 in lung myofibroblasts.
2018-08-09 | GSE110408 | GEO
Project description:The objective of this study was to understand the impact of losing cadherin-11 (CDH11) on kidney injury. CDH11 has previously been demonstrated to be associated with a number of fibrotic diseases, but its role in kidney injury remains unknown. In vivo models of kidney injury demonstrated improved renal function and reduced tubulointerstitial fibrosis with CDH11 inhibition. However, the mechanism by which CDH11 inhibition mitigates kidney injury is unknown. RNAseq analysis showed altered expression of over 50 genes in two models of kidney injury when CDH11-/- mice were compared with CDH11+/+ mice. These results together indicate that CDH11 deletion alters many genes and pathways that could contribute to kidney injury, including alpha-1 antitrypsin, which is increased in CDH11-/- mice and has been shown to be beneficial in kidney injury.
2024-11-26 | GSE189680 | GEO
Project description:The objective of this study was to understand the impact of losing cadherin-11 (CDH11) on kidney injury. CDH11 has previously been demonstrated to be associated with a number of fibrotic diseases, but its role in kidney injury remains unknown. In vivo models of kidney injury demonstrated improved renal function and reduced tubulointerstitial fibrosis with CDH11 inhibition. However, the mechanism by which CDH11 inhibition mitigates kidney injury is unknown. RNAseq analysis showed altered expression of over 50 genes in two models of kidney injury when CDH11-/- mice were compared with CDH11+/+ mice. These results together indicate that CDH11 deletion alters many genes and pathways that could contribute to kidney injury, including alpha-1 antitrypsin, which is increased in CDH11-/- mice and has been shown to be beneficial in kidney injury.
2024-11-26 | GSE189681 | GEO
Project description:The objective of this study was to understand the impact of losing cadherin-11 (CDH11) on the immune response in atherosclerosis. CDH11 has previously been demonstrated to be associated with a number of fibrotic diseases, but its exact role in inflammation remains relatively unknown. In vivo models of atherosclerosis demonstrated altered immune cell profiles with CDH11-deficiency, including decreased circulating myeloid cell populations. In vitro studies of CDH11-deficient macrophages revealed increased expression of genes associated with migration, despite a functional decrease in migration, possibly due to compensatory mechanisms. RNAseq analysis also showed increased expression of MHC class II molecule genes in CDH11-/- macrophages, indicating that loss of CDH11 in macrophages could alter T cell populations through increased activation of CD4+ helper T cells. These results together indicate that CDH11 can alter the immune response, in part by impairing macrophage migration and by affecting T cell activation.
2021-09-26 | GSE165942 | GEO
Project description:The goal of this experiment was to identify if there are any genes differentially expressed in Cadherin-11 KD HIMF
2021-05-07 | GSE173973 | GEO
Project description:Background & Aims: Pancreatic ductal adenocarcinomas (PDAC) are characterized by fibrosis and an abundance of cancer-associated fibroblasts (CAFs). We investigated strategies to disrupt interactions among CAFs, the immune system, and cancer cells, focusing on adhesion molecule cadherin 11 (CDH11), which has been associated with other fibrotic disorders and is expressed by activated fibroblasts. Methods: We compared levels of CDH11 mRNA in human pancreatitis and pancreatic cancer tissues and cells, compared with normal pancreas, and measured levels of CDH11 protein in human and mouse pancreatic lesions and normal tissues. We crossed p48-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ (KPC) mice with CDH11-knockout mice and measured survival times of offspring. Pancreata were collected and analyzed by histology, immunohistochemistry, and (single-cell) RNA sequencing; RNA and proteins were identified by imaging mass cytometry. Some mice were given injections of PD1 antibody or gemcitabine and survival was monitored. Pancreatic cancer cells from KPC mice were subcutaneously injected into Cdh11+/+ and Cdh11–/– mice and tumor growth was monitored. Pancreatic cancer cells (mT3) from KPC mice (C57BL/6), were subcutaneously injected into Cdh11+/+ (C57BL/6J) mice and mice were given injections of antibody against CDH11, gemcitabine, or small molecule inhibitor of CDH11 (SD133) and tumor growth was monitored. Results: Levels of CDH11 mRNA and protein were significantly higher in CAFs than in pancreatic cancer epithelial cells, human or mouse pancreatic cancer cell lines, or immune cells. KPC/Cdh11+/– and KPC/Cdh11–/– mice survived significantly longer than KPC/Cdh11+/+ mice. Markers of stromal activation entirely surrounded pancreatic intraepithelial neoplasias in KPC/Cdh11+/+ mice and incompletely in KPC/Cdh11+/– and KPC/Cdh11–/– mice, whose lesions also contained fewer FOXP3+ cells in the tumor center. Compared with pancreatic tumors in KPC/Cdh11+/+ mice, tumors of KPC/Cdh1+/– mice had increased markers of antigen processing and presentation; more lymphocytes and cytokines associated with lymphocyte infiltration; decreased extracellular matrix components; and reductions in markers and cytokines associated with immunosuppression. Administration of the PD1 antibody did not prolong survival of KPC mice with 0, 1, or 2 alleles of Cdh11. Gemcitabine extended survival only of KPC/Cdh11+/– and KPC/Cdh11–/– mice or reduced subcutaneous tumor growth in mT3 engrafted Cdh11+/+ mice given in combination with the CDH11 antibody. A small molecule inhibitor of CDH11 reduced growth of pre-established mT3 subcutaneous tumors only if T and B cells were present in mice. Conclusions: Knockout or inhibition of CDH11, which is expressed by CAFs in the pancreatic tumor stroma, reduces growth of pancreatic tumors, increases their response to gemcitabine, and significantly extends survival of mice. CDH11 promotes immunosuppression and extracellular matrix deposition, and might be developed as a therapeutic target for pancreatic cancer.
2020-12-01 | GSE157781 | GEO
Project description:Cadherin-11 expression is associated with tumor progression and metastasis in various cancers, including basal-like breast carcinoma and advanced prostate cancer, and invasive cell lines, yet is absent in normal epithelium. We now show cadherin-11 attenuation in aggressive breast and prostate cancer cells results in marked decreases in proliferation, migration, and invasion. Cadherin-11 depletion in MDA-231 cells prevents tumor growth in mice and alters gene expression associated with poor prognosis malignancies. Additionally, a novel small molecule inhibitor targeting its unique adhesive interface significantly inhibits the growth and migration of cadherin-11 positive cells. Cadherin-11 is essential for malignant progression of MDA-231 basal-type cells, and may serve as both an aggressive tumor marker and viable therapeutic target for poor prognosis carcinomas expressing it.
2010-02-22 | GSE14943 | GEO
Project description:FOXF1 inhibits pulmonary fibrosis by preventing CDH2-CDH11 cadherin switch in myofibroblasts
| PRJNA433652 | ENA
Project description:RNA-seq in untreated and Cadherin-11 Knockdown Human Intestinal Myofibroblast cells (HIMF)
| PRJNA727790 | ENA