2026-06-27T23:02:38Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/181112025-08-08T13:57:11Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Blanco Ramos, Francisco 2023-06-17T22:08:01Z 2023-06-17T22:08:01Z 2017 2045-2322 10.1038/s41598-017-03921-4 https://hdl.handle.net/20.500.14352/18111 http://dx.doi.org/10.1038/s41598-017-03921-4 https://www.nature.com/ Increased glycolysis and HIF-1 alpha activity are characteristics of cells under hypoxic or inflammatory conditions. Besides, in normal O-2 environments, elevated rates of glycolysis support critical cellular mechanisms such as cell survival. The purpose of this study was to analyze the contribution of HIF-1 alpha to the energy metabolism and survival of human synovial fibroblasts (SF) under normoxic conditions. HIF-1 alpha was silenced using lentiviral vectors or small-interfering RNA (siRNA) duplexes. Expression analysis by qRT-PCR and western blot of known HIF-1 alpha target genes in hypoxia demonstrated the presence of functional HIF-1 alpha in normoxic SF and confirmed the glycolytic enzyme glyceraldehyde3-phosphate dehydrogenase (GAPDH) as a HIF-1 alpha target even in normoxia. HIF-1 alpha silencing induced apoptotic cell death in cultured SF and, similarly, treatment with glycolytic, but not with OXPHOS inhibitors, induced SF death. Finally, in vivo HIF-1 alpha targeting by siRNA showed a significant reduction in the viability of human SF engrafted into a murine air pouch. Our results demonstrate that SF are highly dependent on glycolytic metabolism and that HIF-1 alpha plays a regulatory role in glycolysis even under aerobic conditions. Local targeting of HIF-1 alpha provides a feasible strategy to reduce SF hyperplasia in chronic arthritic diseases. eng Atribución 3.0 España Hif-1 alpha Knockdown Reduces Glycolytic Metabolism and Induces Cell Death of Human Synovial Fibroblasts Under Normoxic Conditions journal article URL https://docta.ucm.es/bitstreams/75daa754-7bbd-4529-876e-2982dd16678d/download File MD5 e864928741562eb2d9c59364bc261246 2394441 application/pdf BlancoRamosF11libre+CC.pdf URL https://docta.ucm.es/bitstreams/4e090d14-3355-424d-8f08-8be4952a326d/download File MD5 4b193327a0256d86cf7ad6f2ed14cee0 49776 text/plain BlancoRamosF11libre+CC.pdf.txt