2. Academic Validation
  3. STING up-regulates VEGF expression in oxidative stress-induced senescence of retinal pigment epithelium via NF-κB/HIF-1α pathway

STING up-regulates VEGF expression in oxidative stress-induced senescence of retinal pigment epithelium via NF-κB/HIF-1α pathway

  • Life Sci. 2022 Mar 15:293:120089. doi: 10.1016/j.lfs.2021.120089.
Qingqiu Chen 1,  Li Tang 2,  Yi Zhang 3,  Chengyu Wan 1,  Xiuxian Yu 1,  Yuman Dong 1,  Xiaoting Chen 4,  Xueling Wang 5,  Ning Li 5,  Guang Xin 1,  Meixia Zhang 6,  Zhen Chen 1,  Hai Niu 1,  Wen Huang 7
Affiliations

Affiliations

  • 1 Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 2 Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 3 Research Core Facility of West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 4 Animal Experimental Center of West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 5 Integrated Chinese and Western Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 6 Macular Disease Research Laboratory, Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 7 Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: [email protected].
PMID: 35007563 DOI: 10.1016/j.lfs.2021.120089
Abstract

Aim: Aging-related dysfunction of retinal pigment epithelium (RPE) is the main pathogenic factors for pathological angiogenesis due to dysregulated vascular endothelial growth factor (VEGF) in retinal vascular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). However, the molecular mechanism behind the up-regulation of VEGF in senescent RPE is still blurred.

Materials and methods: As oxidative damage is the key cause of RPE dysfunction, we employed a model of oxidative stress-induced premature senescence of ARPE-19 to explore the effect of senescent RPE on VEGF.

Key findings: We reported that senescent ARPE-19 up-regulated VEGF expression under both short-term and prolonged H2O2 treatment, accompanying with increased HIF-1α, the key mediator of VEGF. STING signaling, which could be activated by oxidative stress-damaged DNA, was also observed to be increased in senescent ARPE-19 treated with H2O2. And the inhibition of STING significantly reduced HIF-1α expression to alleviate the up-regulation of VEGF. NF-κB was also shown to be involved in the regulation of VEGF in senescent ARPE-19 in response to STING signaling. Furthermore, oxidative stress impaired the lysosomal clearance of damaged DNA to enhance STING signaling, thereby up-regulating VEGF expression in senescent RPE.

Significance: Our data provide evidence that STING plays an important role in VEGF regulation in senescent RPE induced by oxidative stress.

Keywords

Autophagic flux; Retinal pigment epithelium; STING; Senescence; VEGF.

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