Similar Datasets
Project description:Lipocalin-2 deficiency attenuates acute lung inflammation
| PRJNA814910 | ENA
Project description:Mast cells (MCs) play a pivotal role in multiple primary tumours, but their function remains largely an enigma in metastatic lymph nodes (LNs). Here, using single-cell RNA sequencing data, photoconversion technique, MC-deficient KitW-sh and lipocalin-2 deficient mice, we show that MCs in LNs promote stemness of tumour cells metastasizing to LNs and their further dissemination to distant organs. Mechanistically, lipocalin-2, secreted by LN MCs, facilitates mitochondrial RNA leakage by mitochondrial permeability transition pore (mPTP) opening, which promotes stem cell transcription factor-TFCP2L1 activity by mitochondrial peptide MOTS-c. Aptamer of MOTS-c or lipocalin-2 neutralization inhibit MC-mediated stemness of tumour cells and reduce lung metastasis burden in vivo. Collectively, we uncover the new function of LN MCs and provide an appealing therapeutic strategy for the progression of carcinoma.
2026-06-01 | GSE269107 | GEO
Project description:Mast cells (MCs) play a pivotal role in multiple primary tumours, but their function remains largely an enigma in metastatic lymph nodes (LNs). Here, using single-cell RNA sequencing data, photoconversion technique, MC-deficient KitW-sh and lipocalin-2 deficient mice, we show that MCs in LNs promote stemness of tumour cells metastasizing to LNs and their further dissemination to distant organs. Mechanistically, lipocalin-2, secreted by LN MCs, facilitates mitochondrial RNA leakage by mitochondrial permeability transition pore (mPTP) opening, which promotes stem cell transcription factor-TFCP2L1 activity by mitochondrial peptide MOTS-c. Aptamer of MOTS-c or lipocalin-2 neutralization inhibit MC-mediated stemness of tumour cells and reduce lung metastasis burden in vivo. Collectively, we uncover the new function of LN MCs and provide an appealing therapeutic strategy for the progression of carcinoma.
2026-06-01 | GSE269109 | GEO
Project description:Agricultural industry workers are frequently exposed to harmful dust particles and consequently have a higher risk of developing chronic lung inflammatory conditions such as chronic obstructive pulmonary disease (COPD). Lipocalin-2 (LCN-2) is an innate immune protein with paradoxical roles in both pro- and anti-inflammatory responses at mucosal sites; however, its role in the lung during homeostatic and inflammatory states, such as those induced by inhaled dusts, remain unknown. Here, we investigated the role of LCN-2 in a murine model of organic dust exposure-induced lung inflammation using wildtype C57Bl/6 (WT) and LCN-2 knockout (KO) mice exposed repetitively to extracts of dusts (DE) collected from swine confinement facilities. Repetitive DE exposure consisted of fifteen days of intranasal instillations with and without a three-day recovery period. Through these investigations, we identified an important function of LCN-2 in regulating tissue homeostasis and recovery following inflammatory injury in the lung. Additionally, compartmentalized effects on T cell and macrophage levels were observed in BALF vs. lung tissue in DE-exposed LCN-2 KO mice versus WT mice. Ablation of LCN-2 resulted in deficits in resolving histopathological markers of inflammation, and decreased levels of IL-10 after DE. Exogenous IL-10 administration partially rescued the histopathological markers of inflammation in LCN-2 KO mice after DE exposure. Taken together, these investigations highlight a novel role for LCN-2 in regulating lung homeostasis, inflammation response, and repair following organic dust-induced inflammation that may be mediated, at least in part, by IL-10.
2026-06-01 | GSE254514 | GEO
Project description:Intrahepatic lipocalin 2 promotes liver fibrosis in alcoholic hepatitis
| PRJNA534053 | ENA
Project description:IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we performed single-cell RNA-seq on an acute LPS mouse model of lung inflammation to provide insights into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. We identified neutrophils as a source of IL-36 which provides a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.
2021-01-25 | GSE159161 | GEO
Project description:Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under pre-clinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernable impact on systemic energy homeostasis, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.
2021-02-02 | PXD022682 | Pride
Project description:IGF1R (Insulin-like Growth Factor 1 Receptor) is a ubiquitously expressed transmembrane tyrosine kinase receptor with multiple functions including inflammation. IGF activity maintains human lung homeostasis, being involved in relevant pulmonary diseases with an inflammatory component, such as lung cancer, COPD, asthma and pulmonary fibrosis. Here we examined the role of IGF1R in lung inflammation using mice with a postnatal deficiency of Igf1r and a model of bleomycin(BLM)-induced lung injury. Lung transcriptome analysis of Igf1r-deficient mice showed a general inhibition of transcription of genes related to epigenetics, inflammation/immune response and oxidative stress activity with potential pulmonary protective roles. Early upon intratracheal BLM treatment, mutant mice showed improved survival and milder pulmonary injury and inflammation. Their lungs presented down-regulation of macrophage (Marco/Adgre1), neutrophil-related (Cxcl1/Ly6g), pro-inflammatory (Tnf/Il1b/Il6), endothelial adhesion (Icam1/Pecam1) and alveolar damage (Aqp5/Sftpc) markers and up-regulation of resolution phase markers (Csf1/Il13/Cd209a). Changes in mRNA of IGF system genes were also found, in parallel to a hindered response to hypoxia (Hif1a) and increased expression of the anti-oxidative stress marker Gpx8. These findings identify Igf1r as an important player in oxidative stress and inflammation and suggest that targeting Igf1r may block the inflammatory response in lung diseases with this component.
2017-07-29 | GSE88908 | GEO
Project description:Mast cells (MCs) play a pivotal role in barrier tissues that connect to the external environment, but their distribution and functions in lymph nodes (LNs) remain largely unclear, especially during the tumor progression. Here, using single-cell RNA sequencing (scRNA-seq), photoconversion tumor cell lines, MC-deficient KitW-sh mice and lipocalin-2-deficient mice, we show that MCs in LNs promote the stemness of tumor cells metastasizing to LNs and their further dissemination to distant organs. Mechanistically, lipocalin-2, which is secreted by LN MCs, facilitates the generation of mitochondrial peptide MOTS-c by opening the mitochondrial permeability transition pore (mPTP), which promotes the activity of the stem cell transcription factor TFCP2L1. Aptamers of MOTS-c or lipocalin-2 neutralization inhibit the MC-mediated stemness of tumor cells and reduce lung metastasis. Overall, we reveal the function of LN MCs and identified an appealing therapeutic strategy for tumor metastasis.
2024-12-19 | PXD059036 |
Project description:ATF3 promotes endothelial cell response to acute lung injury
| PRJNA880905 | ENA