Hypoxia-inducible factor-1: A potential pharmacological target to manage psoriasis

Zhu, Wenjing; Li, Ping; Xu, Yangchun

doi:10.1016/j.intimp.2020.106689

Cited by 30 publications

(20 citation statements)

References 48 publications

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“…It has also been studied in the pathophysiology of keratinocytes in psoriasis [8]. Psoriasis is known to be a T-cell-mediat-ed autoimmune skin disease that can affect the skin, even nails, and joints [1,9]. The release of tumor necrosis factor-α (TNF-α), interleukin (IL)-17A, and IL-22 inflammatory cytokines are associated with initial T-cell imbalance.…”

Section: Introductionmentioning

confidence: 99%

MiR-221-3p as a Potential Biomarker for Patients with Psoriasis and Its Role in Inflammatory Responses in Keratinocytes

Meng

Qiu²,

Zhang

2021

Skin Pharmacol Physiol

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Introduction: This study investigated serum miR-221-3p levels in psoriatic patients and the characterization of serum miR-221-3p in keratinocyte inflammatory responses was further assessed. Methods: qRT-PCR was used to detect the expression level of miR-221-3p in the serum of 46 patients with psoriasis and 42 healthy controls. The receiver operating characteristic curve evaluated the diagnostic ability of miR-221-3p in psoriasis. The effect of miR-221-3p on HaCaT cell proliferation was detected by using a cell counting Kit-8 and Transwell. ELISA was used to detect serum and keratinocyte pro-inflammatory factors. Results: miR-221-3p was significantly increased in the serum of patients with psoriasis. The area under the curve was 0.861, the sensitivity was 80.4%, and the specificity was 85.7%. Serum miR-221-3p was positively correlated with the expression levels of tumor necrosis factor-α, interleukin (IL)-17A, and IL-22. Cell experiments showed that reducing the expression of miR-221-3p could significantly inhibit cell proliferation. Additionally, miR-221-3p downregulation also inhibited the release of some inflammatory factors in the HaCaT cells. Discussion/Conclusion: MiR-221-3p is a latent biomarker of psoriasis patients. Lower expression of miR-221-3p inhibits the cell proliferation and inflammatory responses of HaCaT cells, which offers a possible target for the therapeutic interventions of psoriasis.

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Section: Introductionmentioning

confidence: 99%

MiR-221-3p as a Potential Biomarker for Patients with Psoriasis and Its Role in Inflammatory Responses in Keratinocytes

Meng

Qiu²,

Zhang

2021

Skin Pharmacol Physiol

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“…Meanwhile, HIF-1α amounts are elevated in psoriatic lesions 11,12 , and in serum specimens from psoriasis cases. These elevated HIF-1α amounts alongside a high association of HIF-1α upregulation with disease severity suggest a major role for HIF-1α in psoriasis' pathogenetic mechanisms 13 . Therefore, angiogenesis, exaggerated proliferation and in ammatory response might constitute a vicious circle, with HIF-1α helping maintain and amplify this vicious circle.…”

Section: Discussionmentioning

confidence: 99%

Qingre Huoxue Decoction, A Traditional Chinese Herbal Formulation, Impacts Angiogenesis in Psoriasis-Like Skin Through the HIF-1α/Flt-1/VEGF Pathway

Wen

Zhu

et al. 2021

Preprint

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Background: Qingre Huoxue Decoction (QHD), a traditional Chinese medicine (TCM) formulation, could alleviate psoriasis in our previous studies. The present work aimed to assess QHD’s effects on psoriasis and the underpinning mechanism in cultured cells and experimental animals.Methods: The CCK-8 assay was carried out for cell viability assessment. HUVEC migration was assessed by transwell and wound healing assays. QHD-induced suppression of capillary tube formation in HUVECs was detected by tube formation assay. In addition, the imiquimod (IMQ)-induced male BALB/c mouse model of psoriasis was established to examine the Psoriasis Area and Severity Index (PASI) after QHD administration. HIF-1α, Flt-1 and VEGF expression levels in vivo were assessed by immunoblot, qPCR and immunofluorescence. Results: The results showed that QHD dose-dependently reduced viability in HUVECs. In addition, QHD suppressed tube formation in HUVECs at levels below those needed to inhibit HUVECs. Upon QHD administration, HUVEC migration was markedly decreased; QHD effectively prevented the migratory ability of HUVECs, as determined by wound areas at 0h, 12h and 24h, respectively. Finally, QHD starkly downregulated HIF-1α, Flt-1 and VEGF in the IMQ-induced mouse model, at the protein and mRNA levels.Conclusions: In summary, QHD inhibits angiogenesis in cultured cells and mice. HIF-1α/Flt-1/VEGF signaling is important in angiogenesis and psoriasis development. These findings provide a rationale for developing QHD for clinical use against psoriasis.

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“…The organism responds to hypoxic stress by regulating downstream gene expression primarily through hypoxia inducible factor‐1 (HIF‐1) 15 . HIF‐1 is a heterodimeric transcription factor consisting of two subunits, HIF‐1α and HIF‐1β, of which HIF‐1α is the active subunit 16 . In hypoxia, HIF‐1α is stably transferred to the nucleus and forms a heterodimeric complex with HIF‐1β, which regulates the transcription of >150 target genes 17,18 .…”

Section: Introductionmentioning

confidence: 99%

“…15 HIF-1 is a heterodimeric transcription factor consisting of two subunits, HIF-1α and HIF-1β, of which HIF-1α is the active subunit. 16 In hypoxia, HIF-1α is stably transferred to the nucleus and forms a heterodimeric complex with HIF-1β, which regulates the transcription of >150 target genes. 17,18 These include the expression of two specific functional genes: vascular endothelial growth factor (VEGF) and erythropoietin (EPO).…”

mentioning

confidence: 99%

The hypoxia adaptation of small mammals to plateau and underground burrow conditions

Pan

Sun

et al. 2021

Anim Models and Exp Med

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Oxygen is a key factor in the growth, reproduction and metabolism of aerobic organisms 1 and oxygen content varies due to environmental factors, such as temperature, humidity, atmospheric pressure and altitude. 2 O 2 deficiencies may occur in environments of land-living animals such as high altitudes 3 and underground caves. 4 Although mammals are largely intolerant of hypoxia, there are a few rodent species that live in hypoxic niches. These animals have evolved complex physiological and molecular adaptive systems that enable them to survive in hypoxic environments. 5 Low O 2 can lead to an increase in the production of reactive oxygen species (ROS) in the organism, 6 which in turn triggers oxidative stress. 7,8 However, antioxidant defense systems in organisms can counteract the adverse effects of ROS. 9 Maintaining a balance between energy production and consumption is also key to tolerating hypoxia. 10,11 In general, in order to adapt to hypoxia, animals can produce energy through anaerobic metabolism to maintain their metabolism, 12 and when the O 2 supply is limited, the metabolic rate of most hypoxiatolerant animals shows a strong decline. 5,13 In hypoxia-tolerant newborn mammals, oxygen consumption (VO 2 ) was shown not to exceed the baseline level during reoxygenation after hypoxia (15% O 2 ), and rapidly returned to the pre-hypoxia level, and lactate accumulation was observed only in more severe hypoxia (10% O 2 ). 14

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Hypoxia-inducible factor-1: A potential pharmacological target to manage psoriasis

Cited by 30 publications

References 48 publications

MiR-221-3p as a Potential Biomarker for Patients with Psoriasis and Its Role in Inflammatory Responses in Keratinocytes

MiR-221-3p as a Potential Biomarker for Patients with Psoriasis and Its Role in Inflammatory Responses in Keratinocytes

Qingre Huoxue Decoction, A Traditional Chinese Herbal Formulation, Impacts Angiogenesis in Psoriasis-Like Skin Through the HIF-1α/Flt-1/VEGF Pathway

The hypoxia adaptation of small mammals to plateau and underground burrow conditions

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