Loss of LOXL2 promotes uterine hypertrophy and tumor progression
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ABSTRACT:
PROVIDER: PRJNA882816 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression microarray was used to evaluate altered genes related to LOXL2 expression level in order to identify potential molecular mechanism in uterus.
2022-09-23 | GSE213868 | GEO
Project description:Temporomandibular joint (TMJ) osteoarthritis (OA) affects a significant population, and there are no FDA-approved drugs for its treatment. Our previous studies showed that lysyl oxidase-like-2 (LOXL2) has anabolic effects on cartilage; however, whether LOXL2 plays a role in relieving TMJ-OA remains unknown. The goal of this study was to comprehensively investigate LOXL2 mechanism in TMJ protection, with an emphasis on transcriptomic network analysis, mitochondria, and apoptosis during TMJ-OA. We showed that the TMJ is transcriptionally unique compared to the knee, with elevated Loxl2 expression and cartilage-degenerative genes, potentially indicating its different mechanisms of action. Aggrecan promoter-specific homozygous deletion of Loxl2 in mice resulted in a cartilage-degeneration phenotype, mitochondrial dysfunction, NF-κβ-mediated chondrocyte apoptosis, and inflammatory immune response leading to TMJ-OA-like conditions. IL-1β is known to induce osteoarthritis via NF-κβ. With regard to translation, adenoviral-Loxl2 transduction in ex-vivo goat cartilage reduced the IL-1β-mediated degenerative effects. Importantly, LOXL2 preserved IL-1β–induced mitochondrial dysfunction, p62-mediated mitophagy, apoptosis, and extracellular matrix degeneration. Overall, we identified the protective role of LOXL2 during natural TMJ-OA-like progression and established LOXL2 as a potential candidate gene therapy candidate for future therapeutics.
2026-02-11 | GSE276978 | GEO
Project description:Temporomandibular joint (TMJ) osteoarthritis (OA) affects a significant population, and there are no FDA-approved drugs for its treatment. Our previous studies showed that lysyl oxidase-like-2 (LOXL2) has anabolic effects on cartilage; however, whether LOXL2 plays a role in relieving TMJ-OA remains unknown. The goal of this study was to comprehensively investigate LOXL2 mechanism in TMJ protection, with an emphasis on transcriptomic network analysis, mitochondria, and apoptosis during TMJ-OA. We showed that the TMJ is transcriptionally unique compared to the knee, with elevated Loxl2 expression and cartilage-degenerative genes, potentially indicating its different mechanisms of action. Aggrecan promoter-specific homozygous deletion of Loxl2 in mice resulted in a cartilage-degeneration phenotype, mitochondrial dysfunction, NF-κβ-mediated chondrocyte apoptosis, and inflammatory immune response leading to TMJ-OA-like conditions. IL-1β is known to induce osteoarthritis via NF-κβ. With regard to translation, adenoviral-Loxl2 transduction in ex-vivo goat cartilage reduced the IL-1β-mediated degenerative effects. Importantly, LOXL2 preserved IL-1β–induced mitochondrial dysfunction, p62-mediated mitophagy, apoptosis, and extracellular matrix degeneration. Overall, we identified the protective role of LOXL2 during natural TMJ-OA-like progression and established LOXL2 as a potential candidate gene therapy candidate for future therapeutics.
2026-02-11 | GSE277139 | GEO
Project description:Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired. 12 samples were analyzed: mES transduced with control shRNA (n=3); mES transduced with LOXL2 shRNA (n=3), ES transduced with control shRNA and treated with RA (n=3); ES transduced with LOXL2 shRNA and treated with RA (n=3)
2015-12-21 | E-GEOD-65675 | biostudies-arrayexpress
Project description:Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired.
2015-12-21 | GSE65675 | GEO
Project description:Progression of uterine aging in mice
| PRJNA1260992 | ENA
Project description:Traumatic knee injuries lead to cartilage degeneration and osteoarthritis (OA). Cartilage has limited potential for self-regeneration, and any damage can lead to structural, molecular, and functional aberrations in the knee joint. Early changes in extracellular matrix (ECM) affecting cartilage are primarily asymptomatic and progress towards knee joint dysfunction, pre-OA, and finally OA. This study aimed to elucidate the mechanism of lysyl oxidase-like 2 (LOXL2) in maintaining healthy knee joint articular cartilage, its regeneration, and potential therapeutic applications. LOXL2 loss-of-function was evaluated using Acan promoter-specific inducible Loxl2 knockout, followed by immunohistochemistry, RNA-seq, transcriptional analysis, and knee joint functional and pain analysis. Our results showed that LOXL2 deletion increases the severity of destabilized medial meniscus (DMM) -induced cartilage damage. LOXL2-overexpressing mice were protected against degenerative cartilage changes in the knee joint compared with their wild-type littermates. Interestingly, Intra-articular injection of adenovirus-delivered LOXL2 protected knee joint function, alleviated cartilage degeneration, restored treadmill running capability, and reduced allodynia. Overall, LOXL2 loss initiates cartilage damage, inflammation, and pain, leading to OA. The gain of LOXL2 protects against progressive cartilage damage and relieves pain and inflammation. Thus, we identified a novel function for LOXL2 in OA-related local pain.
2026-01-21 | GSE285114 | GEO
Project description:LOXL2 protects temporomandibular joint from mitochondrial dysfunction, apoptosis and osteoarthritis like progression
| PRJNA1159874 | ENA
Project description:Triple-negative breast cancer (TNBC) often develops resistance to single-agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B-MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co-inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4-MED1 colocalization, and the transcription of cell cycle genes, thus supressing TNBC cell proliferation. Finding novel strategies to disrupt BRD4S-LOXL2 interaction holds potential for developing successful TNBC therapies.
2022-03-18 | GSE198647 | GEO
Project description:Spinal-cord injury in mammals causes permanent loss of sensory and motor function due to scar formation obstructing axon regrowth. In contrast, zebrafish fully regenerate their spinal cord without lasting fibrosis. Here, we identify the transcription factor GATA4 as a key regulator of regeneration. After injury, Gata4 is primarily upregulated in dorsal ependymo-radial glial cells (ERGs). GATA4 preserves glial identity and orchestrates regenerative extracellular matrix (ECM) remodeling. GATA4 loss biases ERGs toward a fibroblast-like state with upregulated Loxl2, a collagen cross-linking enzyme, and can also increase Loxl2 in surrounding non-glial cells. Excess Loxl2 activity promotes pathological crosslinking and formation of a rigid, fibrotic matrix impairing glial and axonal bridging across the lesion, greatly reducing motor recovery. Pharmacological inhibition of Loxl2 in gata4 mutants substantially rescues ECM organization, tissue bridging, and functional recovery. Injury-induced Gata4 activation depends on a short hypoxia-responsive enhancer and is driven, at least in part, by Hif1a signaling. We identify the Gata4–Loxl2 axis as a central regulator of and potential therapeutic target for scar-free spinal-cord repair.
2026-08-11 | GSE316679 | GEO