{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Woods PS"],"funding":["NIEHS NIH HHS","NHLBI NIH HHS","U.S. Department of Defense"],"pagination":["11574"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11971270"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["HIF-1α plays a critical role in shaping macrophage phenotype and effector function. We have previously shown that tissue-resident alveolar macrophages (TR-AMs) have extremely low glycolytic capacity at steady-state but can shift toward glycolysis under hypoxic conditions. Here, we generated mice with tamoxifen-inducible myeloid lineage cell specific deletion of Hif1a (Hif1a<sup>fl/fl</sup>:LysM-CreERT2<sup>+/-</sup>) and from these mice, we isolated TR-AMs and bone marrow-derived macrophages (BMDMs) in which Hif1a is deleted. We show that TR-AM HIF-1α is required for the glycolytic shift under prolyl hydroxylase inhibition but is dispensable at steady-state for inflammatory effector function. In contrast, HIF-1α deletion in BMDMs led to diminished glycolytic capacity at steady-state and reduced inflammatory capacity, but higher mitochondrial function. Gene set enrichment analysis revealed enhanced c-Myc transcriptional activity in Hif1a<sup>-/-</sup> BMDMs, and upregulation of gene pathways related to ribosomal biogenesis and cellular proliferation. We conclude that HIF-1α regulates mitochondrial function in BMDMs but not in TR-AMs. The findings highlight the heterogeneity of HIF-1α function in distinct macrophage populations and provide new insight into how HIF-1α regulates gene expression, inflammation, and metabolism in different types of macrophages."],"journal":["Scientific reports"],"pubmed_title":["HIF-1 regulates mitochondrial function in bone marrow-derived macrophages but not in tissue-resident alveolar macrophages."],"pmcid":["PMC11971270"],"funding_grant_id":["R01 HL151680","HT9425-24-1-0138","T32 HL007605","F32 HL167569","R01HL151680","T32HL007605","R01 ES015024","R01ES015024","F32HL167569"],"pubmed_authors":["Woods PS","Haugen B","Hamanaka RB","Shin KWD","Tian Y","Shamaa OR","Cetin-Atalay R","Mutlu GM","Meliton AY","Sun KA"],"additional_accession":[]},"is_claimable":false,"name":"HIF-1 regulates mitochondrial function in bone marrow-derived macrophages but not in tissue-resident alveolar macrophages.","description":"HIF-1α plays a critical role in shaping macrophage phenotype and effector function. We have previously shown that tissue-resident alveolar macrophages (TR-AMs) have extremely low glycolytic capacity at steady-state but can shift toward glycolysis under hypoxic conditions. Here, we generated mice with tamoxifen-inducible myeloid lineage cell specific deletion of Hif1a (Hif1a<sup>fl/fl</sup>:LysM-CreERT2<sup>+/-</sup>) and from these mice, we isolated TR-AMs and bone marrow-derived macrophages (BMDMs) in which Hif1a is deleted. We show that TR-AM HIF-1α is required for the glycolytic shift under prolyl hydroxylase inhibition but is dispensable at steady-state for inflammatory effector function. In contrast, HIF-1α deletion in BMDMs led to diminished glycolytic capacity at steady-state and reduced inflammatory capacity, but higher mitochondrial function. Gene set enrichment analysis revealed enhanced c-Myc transcriptional activity in Hif1a<sup>-/-</sup> BMDMs, and upregulation of gene pathways related to ribosomal biogenesis and cellular proliferation. We conclude that HIF-1α regulates mitochondrial function in BMDMs but not in TR-AMs. The findings highlight the heterogeneity of HIF-1α function in distinct macrophage populations and provide new insight into how HIF-1α regulates gene expression, inflammation, and metabolism in different types of macrophages.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2025-07-07T03:10:01.761Z","creation":"2025-07-07T03:10:01.761Z"},"accession":"S-EPMC11971270","cross_references":{"pubmed":["40185846"],"doi":["10.1038/s41598-025-95962-3"]}}