Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66948 | GEO | 2016/03/07
SECONDARY ACCESSION(S): PRJNA278455
REPOSITORIES: GEO
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Project description:Developmental dysplasia of the hip (DDH) is one of the significant risk factors for hip osteoarthritis. In order to investigate the factors that induce early articular cartilage degeneration of the hip joints that are exposed to reduced dynamic loads arising from hip dislocation , we created rodent models of hip dislocation by swaddling. Notably, expression of periostin (Postn) was increased in the acetabular articular cartilage of the DDH models; Postn was a candidate gene associated with early articular cartilage degeneration. We showed that early articular cartilage degeneration was suppressed in Postn-/- DDH mice. Furthermore, a microgravity environment induced the expression of Postn in chondrocytes through STAT3 signaling. Postn induced catabolic factors, interleukin-6 and matrix metalloproteinase 3, in articular chondrocytes through integrin-nuclear factor κB signaling. Additionally, interleukin-6 stimulated Postn expression through STAT3 signaling. Thus, Postn plays a critical role in early articular cartilage degeneration associated with hip dislocation.
2022-07-20 | GSE173637 | GEO
Project description:Periostin, a matricellular protein, has been reported to be important in supporting tumor cell dissemination. However, the molecular mechanisms underlying periostin function within the tumor microenvironment are poorly understood. In this study, we observe that loss of periostin decreases esophageal squamous cell carcinoma (ESCC) tumor growth in vivo and demonstrate that periostin cooperates with a conformational missense p53 mutation to enhance invasion. Pathway analyses reveal that invasive esophageal cells expressing periostin and p53R175H mutation display activation of signal transducer and activator of transcription 1 (STAT1) target genes, suggesting that the induction of STAT1 and STAT1-related genes could foster a permissive microenvironment that facilitates invasion of esophageal epithelial cells into the extracellular matrix (ECM). Genetic knockdown of STAT1 in transformed esophageal epithelial cells underscores the importance of STAT1 in promoting invasion and potentiate tumor resistance to genotoxic stress. Furthermore, we find that STAT1 is activated in ESCC xenograft tumors but this activation is attenuated with inducible knockdown of periostin in ESCC tumors. Overall, these results highlight the molecular mechanisms supporting the capacity of periostin in mediating tumor invasion during ESCC development. Pre-clinical study hTERT: EPC cells immortalized by expression of hTERT hTERT_p53: EPC cells expressing hTERT and mutant P53 hTERT_p53_POSTN: EPC cells expressing hTERT, mutant P53, and POSTN.
2016-06-01 | E-GEOD-48999 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease with only three to five years of the median survival. Fibroblast proliferation is a hallmark of IPF as well as secretion of extracellular matrix proteins from fibroblasts. However, it is still uncertain how IPF fibroblasts acquire the ability to progressively proliferate. Periostin is a matricellular protein that is highly expressed in the lung tissues of IPF patients and plays a critical role in the pathogenesis of pulmonary fibrosis. However, it remains undetermined whether periostin affects proliferation of lung fibroblasts. In this study, we first comprehensively tried to identify periostin-dependently expressed genes in lung fibroblasts finding that many cell-cycle–related genes are involved in the gene profile. We confirmed that periostin silencing downregulates expression of several cell-cycle–related molecules including the cyclin family, the CDK family, the E2F family, and the transcriptional factors such as B-MYB and FOXM1 in lung fibroblasts. Accordingly, periostin silencing slowed proliferation of lung fibroblasts and affects the distribution of cell cycle particularly at the G1/S checkpoint and drives the cells into G1 arrest. Lung fibroblasts derived from IPF patients also required periostin for maximum proliferation. Moreover, CP4715, a potent inhibitor against integrin V3, a periostin receptor, downregulated proliferation along with expression of cell-cycle–related genes in IPF lung fibroblasts as well as normal lung fibroblasts. These results demonstrate that periostin plays a critical role in proliferation of lung fibroblasts and provide us a beneficial basis to apply the inhibitors against the periostin/integrin V3 interaction to IPF patients.
2020-04-14 | GSE132917 | GEO
Project description:Abnormal mechanical load is a main risk factor of intervertebral disc degeneration (IDD), and cellular senescence is a pathological change in IDD. Additionally, extracellular matrix (ECM) stiffness promotes human nucleus pulposus cells (hNPCs) senescence. However, the molecular mechanism underlying mechano-induced cellular senescence and IDD progression is not yet fully elucidated. First, we demonstrated that mechano-stress promoted hNPCs senescence via NF-κB signaling. Subsequently, we identified periostin as the main mechano-responsive molecule in hNPCs through unbiased sequencing, which was transcriptionally upregulated by NF-κB p65; moreover, secreted periostin by senescent hNPCs further promoted senescence and upregulated the catabolic process in hNPCs through activating NF-κB, forming a positive loop. Both Postn (encoding periostin) knockdown via siRNA and periostin inactivation via neutralizing antibodies alleviated IDD and NPCs senescence. Furthermore, we found that mechano-stress initiated the positive feedback of NF-κB and periostin via PIEZO1. PIEZO1 activation by Yoda1 induced severe IDD in rat tails without compression, and Postn knockdown alleviated the Yoda1-induced IDD in vivo. Here, we reported for the first time that self-amplifying loop of NF-κB and periostin initiated via PIEZO1 under mechano-stress accelerated NPCs senescence, leading to IDD. Furthermore, periostin neutralizing antibodies, which may serve as potential therapeutic agents for IDD, interrupted this loop.
2022-06-06 | GSE185728 | GEO
Project description:During the postnatal period in mammals, the cardiac muscle transitions from hyperplasic to hypertrophic growth, the extracellular matrix (ECM) undergoes remodeling, and the heart loses regenerative capacity. While ECM maturation and crosstalk between cardiac fibroblasts (CFs) and cardiomyocytes (CM) have been implicated in neonatal heart development, not much is known about specialized fibroblast heterogeneity and functions in the early postnatal period. In order to better understand CF functions in heart maturation and postnatal cardiomyocyte cell cycle arrest, we have performed gene expression profiling and ablation of postnatal CF subpopulations. Fibroblast lineages expressing Tcf21 or Periostin were traced in transgenic GFP reporter mice and their biological functions and transitions during the postnatal period were examined in sorted cells using RNAseq. A subpopulation of highly proliferative Periostin (Postn)+ CFs was found from postnatal day (P)1 to P11 but was not detected at P30. This population was less abundant and transcriptionally different from Tcf21+ resident CFs, which persist in the mature heart. The Postn+ subpopulation preferentially expresses genes related to cell proliferation and neuronal development, while Tcf21+ CFs differentially express genes related to ECM maturation at P7 and immune crosstalk at P30. Ablation of the Postn+ CFs from P0 to P6 led to altered cardiac sympathetic nerve patterning and a reduction in CM binucleation, maturation, and hypertrophic growth. Thus, postnatal CFs are heterogeneous and include a transient proliferative Postn+ subpopulation required for cardiac nerve development and cardiomyocyte maturation soon after birth.
2020-08-05 | GSE144587 | GEO
Project description:We compared transcriptional differences between Periostin siRNA treated and GFP-siRNA treated in OP9 cells using Affymetrix mouse 430_2 array.
2012-01-26 | E-MTAB-519 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized as progressive and irreversible fibrosis in the interstitium of lung tissues. There is still an unmet need to develop a novel therapeutic drug for IPF. We have previously demonstrated that periostin, a matricellular protein, plays an important role in the pathogenesis of pulmonary fibrosis. However, the underlying mechanism of how periostin causes pulmonary fibrosis remains unclear. In this study, we sought to see whether the cross-talk between transforming growth factor-b (TGF-b), a central mediator in the pathogenesis of pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether taking advantage of the cross-talk between TGF-b and periostin, inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in the model mice. We found that there exists a cross-talk between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is important for expression of several downstream molecules of TGF-b including serpin family E member 1, CCN family member 2/connective tissue growth factor, insulin-like growth factor binding protein-3, and IL-11, all of which have been already shown to be important for pulmonary fibrosis. We, moreover, found several potent integrin inhibitors to block the cross-talking with TGF-b signals and CP4715, one of the compounds, improved bleomycin-induced pulmonary fibrosis in mice. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block the cross-talk between TGF-b and periostin.
2019-09-17 | GSE124781 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized as progressive and irreversible fibrosis in the interstitium of lung tissues. There is still an unmet need to develop a novel therapeutic drug for IPF. We have previously demonstrated that periostin, a matricellular protein, plays an important role in the pathogenesis of pulmonary fibrosis. However, the underlying mechanism of how periostin causes pulmonary fibrosis remains unclear. In this study, we sought to see whether the cross-talk between transforming growth factor-b (TGF-b), a central mediator in the pathogenesis of pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether taking advantage of the cross-talk between TGF-b and periostin, inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in the model mice. We found that there exists a cross-talk between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is important for expression of several downstream molecules of TGF-b including serpin family E member 1, CCN family member 2/connective tissue growth factor, insulin-like growth factor binding protein-3, and IL-11, all of which have been already shown to be important for pulmonary fibrosis. We, moreover, found several potent integrin inhibitors to block the cross-talking with TGF-b signals and CP4715, one of the compounds, improved bleomycin-induced pulmonary fibrosis in mice. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block the cross-talk between TGF-b and periostin.
2019-09-17 | GSE124780 | GEO
Project description:We have found that thyroid hormones (THs), acting as soluble integrin αvβ3 ligands, activate growth-related signaling pathways in T-cell lymphomas (TCL). Specifically, TH-activated αvβ3 integrin signaling promotes TCL proliferation and angiogenesis, in part, via the up-regulation of VEGF.
2015-02-18 | GSE63122 | GEO
Project description:Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell-type in terms of their origins and functional effects in vivo. Methods: Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen inducible Cre for cellular lineage tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Results: Lineage tracing with 4 additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin+ myofibroblasts reduces collagen production and scar formation after myocardial infarction. Periostin-traced myofibroblasts also revert back to a less activated state upon injury resolution. Conclusions: Our results define the myofibroblast as a periostin-expressing cell-type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21+ tissue-resident fibroblasts. Fluidigm C1 whole genome transcriptome analysis of lineage mapped cardiac myofibroblasts
2016-06-14 | E-GEOD-83337 | biostudies-arrayexpress