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Frontiers of Medicine 2007年第1期1卷 79-86页

作者： LI Yanhua BI Zhigang Department of Dermatology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

The aim of this research was to explore the effects and signaling pathway of ultraviolet-B(UVB)irradiation on the expression of hypoxia-inducible factor 1a(HIF-1α)and transferrin receptor(TfR).HIF-1α protein was measured by Western blot *** of epidermal growth factor receptor(EGFR),phosphor-EGF-R and TfR after UVB irradiation were determined with flow *** UVB irradiation,mRNA levels of HIF-1α and TfR were detected by real *** showed that compared with control groups,UVB was able to induce HIF1α and TfR protein expression in a dose-and time-dependent manner in HaCat cells(P0.05).The EGFR/PI3K/AKT signaling pathway was required for the induction of HIF-1α and TfR expression induced by *** induced activation of EGFR in HaCat cells and EGFR regulated expression of TfR and HIF-1α.EGFR(−/−)MEF did not increase the HIF1 expression following UVB irradiation(P>0.05).In contrast,EGFR(+/+)MEF strongly enhanced HIF1a expression after UVB irradiation(P0.05).In contrast,DEC1(+/+)HaCat cells strongly enhanced TfR and HIF-1α protein expression after UVB irradiation(P<0.05).We conclude that UVB induces TfR and HIF-1α expressions via EGFR/PI3K/AKT/DEC1 signaling pathway.

关键词： ultraviolet-B hypoxia-inducible factor 1α receptors,transferrin receptors,epidermal growth factor phosphatidylinositol-3-kinase DEC1

Increased hypoxia-inducible factor 1alpha expression in rat brain tissues in response to aging

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Neural Regeneration Research 2012年第10期7卷 778-782页

作者： Huqing Wang Haiqin Wu Hena Guo Guilian Zhang Ru Zhang Shuqin Zhan Department of Neurology Second Affiliated Hospital of Medical College Xi＇an Jiaotong University Xi＇an 710004 Shaanxi Province China

The present study observed changes in rat neural cells at various ages （3, 18, 24, and 30 months）. With age, neural cells became large and were sparsely arranged, and the number of Nissl bodies decreased. In addition, hypoxia-inducible factor 1α expression increased with increasing age in hippocampal CA1 and CA3 regions, motor cortex, and the first subfolium, especially from 3 to 18 months. In the open-field test, grid crossing decreased with increasing age, especially from 18 months. The number of rearings reached a peak in the 18 months group, and then subsequently decreased. The results suggested that hypoxia-inducible factor 1α played an important role in the nervous system aging process.

关键词： aging brain hypoxia-inducible factor 1α Nissl body behavior

Early expressions of hypoxia-inducible factor 1alpha and vascular endothelial growth factor increase the neuronal plasticity of activated endogenous neural stem cells after focal cerebral ischemia

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Neural Regeneration Research 2014年第9期9卷 912-918页

作者： Seung Song Jong-Tae Park Joo Young Na Man-Seok Park Jeong-Kil Lee Min-Cheol Lee Hyung-Seok Kim Department of Forensic Medicine Chonnam National University Medical School Department of Neurology Chonnam National University Medical School Department of Neurosurgery Chonnam National University Medical School Department of Pathology Chonnam National University Medical School

Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine（BrdU） incorporation. hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial gr

关键词： nerve regeneration brain ischemia neural stem cell neural precursor cell hypoxia-inducible factor 1α vascular endothelial growth factor microenvironment photothrombosis neural regeneration

hypoxia-inducible factor-1α–mediated upregulation of CD99 promotes the proliferation of placental mesenchymal stem cells by regulating ERK1/2

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World Journal of Stem Cells 2021年第4期13卷 317-330页

作者： Xu-Dong Feng Jia-Qi Zhu Jia-Hang Zhou Fei-Yan Lin Bing Feng Xiao-Wei Shi Qiao-Ling Pan Jiong Yu Lan-Juan Li Hong-Cui Cao State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND As human placenta-derived mesenchymal stem cells(hP-MSCs)exist in a physiologically hypoxic microenvironment,various studies have focused on the influence of ***,the underlying mechanisms remain to be further *** The aim was to reveal the possible mechanisms by which hypoxia enhances the proliferation of *** A hypoxic cell incubator(2.5%O2)was used to mimic a hypoxic *** counting kit-8 and 5-ethynyl-20-deoxyuridine incorporation assays were used to assay the proliferation of *** cell cycle was profiled by flow *** profiling of hP-MSCs under hypoxia was performed by RNA ***99 mRNA expression was assayed by reverse transcription-polymerase chain *** interfering RNA-mediated hypoxia-inducible factor 1α(HIF-1α)or CD99 knockdown of hP-MSCs,luciferase reporter assays,and the ERK1/2 signaling inhibitor PD98059 were used in the mechanistic *** expression was assayed by western blotting;immunofluorescence assays were conducted to evaluate changes in expression *** hypoxia enhanced hP-MSC proliferation,increased the expression of cyclin E1,cyclin-dependent kinase 2,and cyclin A2,and decreased the expression of *** hypoxia,CD99 expression was increased by HIF-1α.CD99-specific small interfering RNA or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase in cell *** hypoxia promoted hP-MSCs proliferation in a manner dependent on CD99 regulation of the MAPK/ERK signaling pathway in vitro.

关键词： hypoxia-inducible factor 1α hypoxia Mesenchymal stem cells Proliferation CD99 RNA sequencing assay MAPK/ERK signaling pathway

Obstructive sleep apnea aggravates neuroinflammation and pyroptosis in early brain injury following subarachnoid hemorrhage via ASC/HIF-1α pathway

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Neural Regeneration Research 2022年第11期17卷 2537-2543页

作者： Jun Xu Qian Li Chen-Yu Xu Shan Mao Jia-Jia Jin Wei Gu Ying Shi Chun-Fang Zou Liang Ye Department of Respiration Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Respiration Nanjing Yuhua HospitalYuhua Branch of Nanjing First HospitalNanjingJiangsu ProvinceChina

Obstructive sleep apnea can worsen the prognosis of subarachnoid *** r,the underlying mechanism remains *** this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep *** found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid ***,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 *** further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling *** also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 *** findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

关键词： apoptosis associated speck like protein containing a CARD early brain injury hypoxia-inducible factor 1α nucleotide-binding domain and leucine-rich repeat protein 3 obstructive sleep apnea pyroptosis neuroinflammation subarachnoid hemorrhage

Small Hairpin Loop RNA Targeting HIF-1α Down-regulates VEGF and Up-regulates PEDF in Human Retinal Pigment Epithelial Cells under Hypoxic Condition

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2008年第4期28卷 460-464页

作者：肖青曾水清吕明良凌士奇 Department of Ophthalmology Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Ophthalmology People's Hospital of Guangxi Zhuang Autonomous Region Department of Ophthalmology Guangzhou Children Hospital

The aim of this study was to explore the effect of small hairpin loop RNA （shRNA） silencing hypoxia-induced factor 1α （HIF-1α） gene on the expression of vascular endothelial growth factor （VEGF） and pigment epithelium derived factor （PEDF） in human retinal pigment epithelium （RPE） cells under hypoxic condition. Two target sites of HIF-1α mRNA were chosen and two kinds of shRNA were designed and synthesized against the target sites. Then the two kinds of shRNA were transfected into human RPE cells in vitro, respectively. These cells were cultured under hypoxic condition that was simulated by using 150 μmol/L CoCl2. The mRNA expressions of HIF-1α, VEGF and PEDF were tested by semi-quantitative reverse transcription PCR （RT-PCR）. The protein levels of HIF-1α, VEGF and PEDF were analyzed by Western blotting. After the two kinds of HIF-1α-specific shRNA were transfected into RPE cells respectively, the expression of HIF-1α mRNA and the levels of HIF-1α protein were decreased significantly in RPE cells under hypoxic condition. The expression of VEGF mRNA and the levels of protein significantly were also decreased. However, the levels of PEDF protein was significantly increased, but the expression of PEDF mRNA showed no significant changes. In conclusion, HIF-1α-specific shRNA can effectively silence the HIF-1α gene, and consequently down-regulate VEGF and up-regulate PEDF expression against hypoxia. These results reveal that HIF-1 is associated with posttranslational mechanism for down-regulating PEDF under hypoxia and provide an explanation for hypoxia-provoked increases in VEGF/PEDF ratios. These results also suggest that HIF-1 is one of the key cytokines to retinal neovascularization.

关键词： shRNA hypoxia-inducible factor 1α vascular endothelial growth factor pigment epi-thelium derived factor hypoxia retinal pigment epithelium

Reveal more mechanisms of precondition mesenchymal stem cells inhibiting inflammation

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World Journal of Stem Cells 2024年第4期16卷 459-461页

作者： Yi Li Qian-Qian Chen En-Qiang Linghu Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology and Hepatology First Medical Center of Chinese PLA General HospitalBeijing 100853China

hypoxia can get more ability to inhibit *** how it impact on survival time of mesenchymal stem cells(MSCs)is confusing and how preconditioned MSCs inhibiting inflammation are partially *** issues decided the value of ... 详细信息

关键词： Mesenchymal stem cell hypoxia-inducible factor 1α hypoxia Inflammation Macrophage

Expression of hypoxia inducible factor lα and Its Significance in Non-small Cell Lung Cancer

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The Chinese-German Journal of Clinical Oncology 2005年第5期4卷 284-286,324-325页

作者：夏曙于世英袁响林武汉华中科技大学同济医学院附属同济医院肿瘤科 430030

Objective： To explore the expression level and its clinical significance of hypoxia inducible factor 1α （HIF-1α ） in non-small lung cancer. Methods： The expression of HIF-1α was detected in 68 human non-small lung cancer samples by immunohistochemistry. Results：（1） Thirty-nine （57.35%） out of the 68 human non-small lung cancer samples was positive for HIF-1α ; （2） The positive rate of HIF-1α in adenocarcinoma and squamous carcinoma was 54.76% （23/42） and 61.54% （16/26） respectively. No significant difference was found between adenocarcinoma and squamous carcinoma of non-small lung cancer in the expression of HIF-1α （P〉0.05）. The positive rate of HIF-1α in middle-high differentiation was 74.28% （26/35）, significantly higher than in low differentiation （39.39%, 13/33）（P〈0.05）; （3） The positive expression of HIF-1α was not correlated to the sexes, ages, tumor stage and lymph node status. Conclusion： The expression of HIF-1α is higher in non-small lung cancer and is correlated to differentiation.

关键词： non-small hmg cancer hypoxia-inducible factor 1α

In Vitro Antimetastatic Effect of Changweiqing(肠胃清) through Antiinvasion of Hypoxic Colorectal Carcinoma LoVo Cells

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Chinese Journal of Integrative Medicine 2011年第7期17卷 517-524页

作者：李静范忠泽孙珏许建华 Department of Oncology Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Objective：To investigate the in vitro effects and the primary mechanisms of Changweiqing（肠胃清, CWQ）on antimetastasis and antiinvasion of hypoxic colon carcinoma *** addition,to provide experimental evidence for the Chinese medicinal theory of＂strengthening the body＇s resistance to eliminate pathogenic factors＂in the treatment of colorectal cancer,including its invasion and ***：First,CWQ sera were prepared with serum-pharmacology ***,the modified hypoxic chamber was designed and flushed with 5%CO_2 and 95%N_2 at 37℃to induce a hypoxic *** effect of CWQ serum on the viability of LoVo cells was tested with MTT cytotoxicity *** wound model and chamber model were established to estimate the effects of CWQ serum on migration and invasion of LoVo *** model for cell adhesion was established to evaluate the effect of CWQ serum on LoVo cells＇ *** gelatin zymography model was performed to determine the effects of CWQ serum on the activities of matrix metalloproteinase-2 （MMP-2）and matrix metalloproteinase-9（MMP-9）.The effects of CWQ serum on the hypoxia-inducible factor 1α（HIF-1α）nuclear translocation and the mRNA level of vascular endothelial growth factor（VEGF）in LoVo cells were determined by Western blot and reverse transcription-polymerase chain reaction（RT-PCR）analyses, ***：CWQ inhibited LoVo cells＇ migration based on wound healing *** inhibitive effect could reach about 68.00%under hypoxic culture and about 29.87%under normoxic culture when cells were treated with 10%CWQ serum for 24 *** results from both cell invasion and adhesion assays showed that CWQ serum could dose-dependently repress the invasion of LoVo cells and inhibit cells from adhering to extra cellular matrix（ECM）.Under the hypoxic culture condition,RT-PCR analysis showed that 10%CWQ serum had down-regulated the expression of VEGF by 45.87%,and the result of Western blot analysis provided further *** HIF-1αamount

关键词： Changweiqing metastasis hypoxia-inducible factor 1α matrix metalloproteinase vascular endothelial growth factor