PMID- 30587686 OWN - NLM STAT- MEDLINE DCOM- 20190514 LR - 20190514 IS - 1880-4926 (Electronic) IS - 1343-4934 (Linking) VI - 60 IP - 4 DP - 2018 TI - Hypoxia-induced upregulation of angiogenic factors in immortalized human periodontal ligament fibroblasts. PG - 519-525 LID - 10.2334/josnusd.17-0441 [doi] AB - Hypoxia induces complex cellular responses that are mediated by a key transcription factor, hypoxia-inducible factor-1 (HIF-1). HIF-1 promotes production of cytokines and angiogenic factors and contributes to recovery of injured tissues. In the present study, expressions of angiogenin (ANG) and vascular endothelial growth factor (VEGF), which are potent angiogenic factors in mammalian tissues, were examined in immortalized fibroblasts exposed to hypoxia. After 24 h of exposure to hypoxia, ANG and VEGF mRNAs expressions were significantly elevated in periodontal ligament (PDL) fibroblasts but not in embryonic fibroblasts. Hypoxia also increased productions of ANG and VEGF proteins in PDL fibroblasts. HIF-1alpha mRNA expression was not affected by hypoxia in either fibroblast, although HIF-1alpha protein expression was enhanced after exposure to hypoxia. Treatment of PDL fibroblasts with dimethyloxaloylglycine, a prolyl hydroxylase inhibitor that stabilizes the HIF-1alpha protein, significantly increased expressions of ANG and VEGF mRNAs under normoxia. This suggests that stabilization of HIF-1alpha is crucial for upregulation of ANG and VEGF in PDL fibroblasts. These results indicate that, under hypoxic conditions, HIF-1alpha upregulates synthesis of ANG and VEGF in PDL fibroblasts and promotes angiogenesis. FAU - Kifune, Takashi AU - Kifune T AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Ito, Hisanori AU - Ito H AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Ishiyama, Misa AU - Ishiyama M AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Iwasa, Satoko AU - Iwasa S AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Takei, Hiroki AU - Takei H AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Hasegawa, Tomokazu AU - Hasegawa T AD - Department of Pediatric Dentistry, Tokushima University Hospital. FAU - Asano, Masatake AU - Asano M AD - Department of Pathology, Nihon University School of Dentistry. FAU - Shirakawa, Tetsuo AU - Shirakawa T AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. AD - Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry. LA - eng PT - Journal Article PL - Japan TA - J Oral Sci JT - Journal of oral science JID - 9808942 RN - 0 (Cytokines) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (RNA, Messenger) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 3.1.27.- (angiogenin) RN - EC 3.1.27.5 (Ribonuclease, Pancreatic) SB - IM MH - Blotting, Western MH - Cell Line MH - Cells, Cultured MH - Cytokines/metabolism MH - Fibroblasts/*metabolism MH - Fluorescent Antibody Technique MH - Humans MH - *Hypoxia MH - Hypoxia-Inducible Factor 1/*metabolism MH - Periodontal Ligament/*cytology MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction MH - Ribonuclease, Pancreatic/*metabolism MH - Up-Regulation MH - Vascular Endothelial Growth Factor A/*metabolism OTO - NOTNLM OT - HIF-1 OT - angiogenin OT - hypoxia OT - periodontal ligament fibroblasts OT - vascular endothelial growth factor EDAT- 2018/12/28 06:00 MHDA- 2019/05/15 06:00 CRDT- 2018/12/28 06:00 PHST- 2018/12/28 06:00 [entrez] PHST- 2018/12/28 06:00 [pubmed] PHST- 2019/05/15 06:00 [medline] AID - 10.2334/josnusd.17-0441 [doi] PST - ppublish SO - J Oral Sci. 2018;60(4):519-525. doi: 10.2334/josnusd.17-0441.