The cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis
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PROVIDER: PRJNA513470 | ENA |
REPOSITORIES: ENA
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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: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:The cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis [AR2857]
| PRJNA513471 | ENA
Project description:The cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis [AR2819]
| PRJNA513472 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-09-17 | GSE124782 | 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 learn whether the cross-talk between TGF-β (transforming growth factor-β), a central mediator in pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether inhibitors for integrin αVβ3, a periostin receptor, can block pulmonary fibrosis in model mice and the TGF-β signals in fibroblasts from patients with IPF. We found that cross-talk exists between TGF-β and periostin signals via αVβ3/β5 converging into Smad3. This cross-talk is necessary for the expression of TGF-β downstream effector molecules important for pulmonary fibrosis. Moreover, we identified several potent integrin low-molecular-weight inhibitors capable of blocking cross-talk with TGF-β signaling. One of the compounds, CP4715, attenuated bleomycin-induced pulmonary fibrosis in vivo in mice and the TGF-β signals in vitro in fibroblasts from patients with IPF. These results suggest that the cross-talk between TGF-β and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block this cross-talk.
| S-EPMC6993541 | biostudies-literature
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:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of stromal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and stromal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Recent animals models generated in our lab demonstrate clinical phenotypes seen in human fibrotic disease. The mouse model of transforming growth factor-? (TGF?)-induced fibrosis include conditionally expressing TGF? in the lung epithelium under control of the CCSP promoter driving rtTA expression (CCSP/TGF?). This allow the TGF? is only expressed in airway and alveolar epithelial cells and only when mice fed doxycycline (Dox). Similar to PF in humans, TGF? mice on Dox developed a progressive and extensive adventitial, interstitial and pleural fibrosis with a decline in lung mechanics. Thus, the TGF? transgenic mouse is a powerful model to determine lung cell-specific molecular signatures involved in pulmonary fibrosis. In this study, we sought to determine changes in the transcriptome during TGF?-induced pulmonary fibrosis. Our results showed that several pro-fibrotic genes increased in the lungs of TGF? mice. This study demonstrates that WT1 network gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a critical regulator fibrotic lung disease. mRNA profiles of CCSP/- and CCSP/TGFalpha mice treated with Dox
2015-03-07 | E-GEOD-66634 | biostudies-arrayexpress
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:The protein periostin is a matricellular protein that is expressed in connective tissue. It is composed of five globular domains arranged in an elongated structure with an extensive disordered C-terminal tail. Periostin contains eleven cysteine residues, of which one is unpaired, and the rest forms five intra-molecular disulfide bonds. Periostin plays an important role during wound healing and is also involved in driving the inflammatory state in atopic diseases. This study provides a comprehensive biochemical characterization of periostin in human skin and in dermal and pulmonary fibroblasts in vitro. Through the application of Western blotting, co-immunoprecipitation, and LC-MS/MS, we show for the first time that periostin is a disulfide bonded homodimer and engages in a novel disulfide bonded complex with fibronectin both in vivo and in vitro. This inherent characteristic of periostin holds the potential to redefine our approach to exploring and understanding its functional role in future research endeavors.
2025-01-22 | PXD045285 | Pride