Exogenous expression of Lox, Loxl1 and Loxl2 regulate gene expression in primary murine lung fibroblasts.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE89121 | GEO | 2016/10/25
SECONDARY ACCESSION(S): PRJNA350326
REPOSITORIES: GEO
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Project description:Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion. Microarray analysis was performed using GeneChip technology in EVCTs isolated from first trimester human placentae. Gene expression in rosiglitazone-treated primary EVCT cultures was compared with matched untreated controls. A total of 175 probe sets identified differentially regulated genes. One of these genes, lysyl oxidase (LOX) which was up-regulated, was further analyzed. Expression of the LOX family was determined by real time Q-PCR, Western blotting, immunohistochemistry and immunofluorescence. LOX, LOXL and LOXL2 mRNA expression was significantly upregulated in PPARg-activated EVCTs. LOX and LOXL2 protein were present throughout the trophoblast cytoplasm, while LOXL was localized to the nucleus and nucleolus. Cell invasion assays on Matrigel Transwells showed that specific inhibition of LOX activity by M-CM-^_-aminopropionitrile led to an increase in EVCT invasiveness, showing the basal inhibitory effect of LOX and LOX-like in the trophoblastic cells invasion process. Together these results show that LOX family as PPARg-target genes participate to the regulation of trophoblast invasion. Total RNA from EVCT were labelled according to the standard Affymetrix protocol. Five independent targets per treatment vs control were generated and hybridized on a GeneChip.
2013-12-04 | E-GEOD-28426 | biostudies-arrayexpress
Project description:Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion. Microarray analysis was performed using GeneChip technology in EVCTs isolated from first trimester human placentae. Gene expression in rosiglitazone-treated primary EVCT cultures was compared with matched untreated controls. A total of 175 probe sets identified differentially regulated genes. One of these genes, lysyl oxidase (LOX) which was up-regulated, was further analyzed. Expression of the LOX family was determined by real time Q-PCR, Western blotting, immunohistochemistry and immunofluorescence. LOX, LOXL and LOXL2 mRNA expression was significantly upregulated in PPARg-activated EVCTs. LOX and LOXL2 protein were present throughout the trophoblast cytoplasm, while LOXL was localized to the nucleus and nucleolus. Cell invasion assays on Matrigel Transwells showed that specific inhibition of LOX activity by ß-aminopropionitrile led to an increase in EVCT invasiveness, showing the basal inhibitory effect of LOX and LOX-like in the trophoblastic cells invasion process. Together these results show that LOX family as PPARg-target genes participate to the regulation of trophoblast invasion.
2013-12-04 | GSE28426 | GEO
Project description:Our previous studies have found that LOX and LOXL1 were highly upregulated in advanced liver fibrosis; herein, we aimed to investigate the roles of LOX and LOXL1 in hepatic stellate cells.
2021-12-01 | GSE155651 | GEO
Project description:Lysyl oxidase is an extracellular enzyme essential for crosslinking elastin and collagen. Mice that do not express Lox have 60% and 40% reductions in elastin-specific and collagen-specific crosslinks, respectively. Mutations in LOX are associated with thoracic aortic aneurysm and dissection (TAAD). Lysyl oxidase knockout mice dye perinatally with ruptured diaphragm, tortuous arteries, and TAAD This is the first study to analyze the mechanical and genetic changes induced by the absence of lysyl oxidase in the thoracic aorta, and may provide new therapeutic targets relevant for the pathogenesis of thoracic aortic aneurysms and dissections
2016-10-28 | GSE89227 | GEO
Project description:Lysyl oxidase (LOX) is an copper dependent amine oxidase enzyme involved in cross linking of collagens and elastins. Lysyl oxidase propeptide (LOX-PP) is 18 kDa region cleaved during maturation of LOX and its anti-tumorigenic role were studied in various cancers. The effect of LOX-PP overexpression in retinoblastoma cancer cells (Y79) using transient transfection of LOX-PP gene accessed for global gene deregulations. The analysis resulted in RB cancer cell death through deregulation of retinoblastoma in cancer, cell cycle, apoptosis, focal adhesion-PI3K-AKT signaling and DNA repair mechanism pathway. Further validations were done using RT-PCR and western blot analysis. Our results provide evidence that inducing apoptosis through AKT-NFκB signaling.
2019-09-01 | GSE119413 | GEO
Project description:We have identified a new novel spliced variant of Lysyl Oxidase-like 2 (LOXL2), termed LOXL2 delta72, in human oesophageal carcinoma cells (ESCC). To explore the biological function of this variant, the cDNA microarrays was perform to assess the genes expression induced by its over-expression in ESCC KYSE150. We used microarrays to detail the global programmed of genes expression when LOXL2 delta72 over-expressed in KYSE150 cells compared with wild-type LOXL2.
2016-03-28 | GSE53645 | GEO
Project description:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and a frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl- Oxidase-Like 2 (LOXL2) as an EMT player and a poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Identification of new molecular markers in basal breast carcinomas 58 (IDC) infiltrative breast ductal carcinoma samples (Grade 3)
2011-10-20 | E-GEOD-29581 | biostudies-arrayexpress
Project description:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and a frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl- Oxidase-Like 2 (LOXL2) as an EMT player and a poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Identification of new molecular markers in basal breast carcinomas
2011-10-21 | GSE29581 | GEO
Project description:Epithelial-to-Mesenchymal Transition (EMT) is a key process contributing to the aggressiveness of cancer cells. EMT is triggered by activation of different transcription factors collectively known as EMT-TFs. Different cellular cues and cell signalling networks activate EMT at transcriptional and posttranscriptional level in different biological and pathological situations. Among them, overexpression of LOXL2 (lysyl oxidase-like 2) induces EMT independent of its catalytic activity. Remarkably, perinuclear/cytoplasmic accumulation of LOXL2 is a poor prognosis marker of squamous cell carcinomas and is associated to basal breast cancer metastasis by mechanisms no yet fully understood. Here, we report that overexpression of LOXL2 promotes its accumulation in the Endoplasmic Reticulum where it interacts with HSPA5 leading to activation of the IRE1-XBP1-branch of the Unfolded Protein Response (UPR). LOXL2-dependent UPR activation induces the expression of several EMT-TFs: SNAI1, SNAI2, ZEB2 and TCF3 that are direct transcriptional targets of XBP1. Remarkably, inhibition of IRE1 blocks LOXL2-dependent upregulation of EMT-TFs thus hindering EMT induction. LOXL2 relationship to Endoplasmic Reticulum Stress
2017-05-11 | GSE90605 | GEO
Project description:Neonatal hypoxic-ischemic brain damage (HIBD) is initiated by perinatal asphyxia, leading to brain injury triggered by reduced blood and oxygen flow, resulting in neurological impairments such as cerebral palsy, epilepsy, cognitive deficits, and behavioral disorders.Recent insights collectively suggest the important roles of lysyl oxidase (LOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms in HIBD remain elusive.In this study, we found through the study of HIBD rat models and the oxygen-glucose deprivation/re-oxygenation (OGD/R) cell models that LOX significantly increased after HIBD or OGD/R. RNA seq results showed a significant increase in piezo1 after primary neuron OGD/R, and iron death data was also enriched. Moreover, inhibiting LOX or piezo1 can rescue neuronal ferroptosis and further improve cognitive function in rats. In addition, we also found that traumatic acid can inhibit the enzyme activity of LOX and improve a series of pathological features of neuronal damage caused by increased LOX.
2024-09-25 | GSE270560 | GEO