Hypoxia-inducible factor

The distinct pathological and molecular features of kidney cancer in adaptation to oxygen homeostasis render this malignancy an attractive model for investigating hypoxia signalling and potentially developing potent targeted therapies. Hypoxia signalling has a pivotal role in kidney cancer, particularly within the most prevalent subtype, known as renal cell carcinoma (RCC). Hypoxia promotes various crucial pathological processes, such as hypoxia-inducible factor (HIF) activation, angiogenesis, proliferation, metabolic reprogramming and drug resistance, all of which contribute to kidney cancer development, growth or metastasis formation...

Breast cancer (BC) poses a great threat to women's health. Neuronal regeneration related protein (NREP) is a multifunctional protein that is involved in embryonic development, regeneration, and human disease. However, the biological function of NREP in tumors is rarely reported and its role in BC remains unknown. Bioinformatics analysis showed that NREP is highly expressed and closely correlated with poor survival in BC patients. Under hypoxic conditions, NREP was upregulated in BC cells, and this promotion was reversed by hypoxia-inducible factor HIF-1α suppression...

Ischemic heart diseases and cardiomyopathies are characterized by hypoxia, energy starvation and mitochondrial dysfunction. HIF-1 acts as a cellular oxygen sensor, tuning the balance of metabolic and oxidative stress pathways to provide ATP and sustain cell survival. Acting on mitochondria, HIF-1 regulates different processes such as energy substrate utilization, oxidative phosphorylation and mitochondrial dynamics. In turn, mitochondrial homeostasis modifications impact HIF-1 activity. This underlies that HIF-1 and mitochondria are tightly interconnected to maintain cell homeostasis...

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3 O4 -carbon dots complex (Fe3 O4 -CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3 O4 -CDs@Fc nano complex...

This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2 ) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro , CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells...

Protein lactylation is a post-translational modification associated with glycolysis. Although recent evidence indicates that protein lactylation is involved in epigenetic gene regulation, its pathophysiological significance remains unclear, particularly in neoplasms. Herein, we investigated the potential involvement of protein lactylation in the molecular mechanisms underlying benign and malignant pancreatic epithelial tumors, as well as its role in the response of pancreatic cancer (PC) cells to gemcitabine...

BACKGROUND/OBJECTIVES: Hypoxia-inducible factor (HIF)-3α1's role in colorectal cancer (CRC) cells, especially its effects on epithelial-mesenchymal transition (EMT), zinc finger E-box binding homeobox 2 (ZEB2) gene expression, and iron metabolism, remains largely unstudied. This research sought to elucidate these relationships. METHODS: RNA-seq was conducted to investigate the impact of HIF-3α1 overexpression in CRC cells. Dual-luciferase reporter assays assessed the direct targeting of ZEB2 by HIF-3α1...

Since the approval of HIF-PH inhibitors, HIF-PH inhibitors have been used clinically, and many studies and clinical case reports have been reported in Japan. A lot of information has been accumulated on clinical usage. However, HIF-PH inhibitors require careful administration for cancer patients due to their action mechanism through upregulating hypoxia-inducible factors (HIFs) level. In cancer cells, HIFs affect tumor progression and contribute to chemo- and radio-resistance. On the other hand, upregulation of HIFs in immune cells is associated with inflammation and suppress tumor progression...

Anemia in chronic kidney disease (CKD) occurs due to insufficient production of erythropoietin to compensate for the decrease in hemoglobin. Anemia in CKD has traditionally been treated with periodic injections of erythropoiesis-stimulating agents (ESAs), which are recombinant human erythropoietin preparations. Although ESA improved anemia in CKD and dramatically improved the quality of life of patients, there are some patients who are hyporesponsive to ESA, and the use of large doses of ESA in these patients may have a negative impact on patient prognosis...

BACKGROUND: Inflammation and subsequent mitochondrial dysfunction and cell death worsen outcomes after revascularization in ischemic stroke. Receptor-interacting protein kinase 1 (RIPK1) activated dynamin-related protein 1 (DRP1) in a NLRPyrin domain containing 3 (NLRP3) inflammasome-dependent fashion and Hypoxia-Inducible Factor (HIF)-1α play key roles in the process. This study determined how phenothiazine drugs (chlorpromazine and promethazine (C + P)) with the hypothermic and normothermic modality impacts the RIPK1/RIPK3-DRP1 and HIF-1α pathways in providing neuroprotection...

Systemic lupus erythematosus (SLE) is a severe autoimmune disease with significant socioeconomic impact worldwide. Orderly energy metabolism is essential for normal immune function, and disordered energy metabolism is increasingly recognized as an important contributor to the pathogenesis of SLE. Disorders of energy metabolism are characterized by increased reactive oxygen species, ATP deficiency, and abnormal metabolic pathways. Oxygen and mitochondria are critical for the production of ATP, and both mitochondrial dysfunction and hypoxia affect the energy production processes...

Mechanical stimulation as a mimic of drusen formation in the eye increases the expression of angiogenic factors in retinal pigment epithelial (RPE) cells, but the underlying molecular mechanisms remain unclear. We investigated and characterized the effects of mechanical stimulation on the expression of angiogenic factors in RPE cells both in vitro and in a mouse model. Mechanical stimulation increased the expression of vascular endothelial growth factor (VEGF, encoded by VEGFA) and other angiogenesis-related genes in cultured RPE1 cells...

Hypoxia can get more ability to inhibit inflammation. But how it impact on survival time of mesenchymal stem cells (MSCs) is confusing and how preconditioned MSCs inhibiting inflammation are partially known. Those issues decided the value of preconditioned MSCs by hypoxia.

BACKGROUND: Osteoporosis (OP) has become a major public health problem worldwide. Most OP treatments are based on the inhibition of bone resorption, and it is necessary to identify additional treatments aimed at enhancing osteogenesis. In the bone marrow (BM) niche, bone mesenchymal stem cells (BMSCs) are exposed to a hypoxic environment. Recently, a few studies have demonstrated that hypoxia-inducible factor 2alpha (HIF-2α) is involved in BMSC osteogenic differentiation, but the molecular mechanism involved has not been determined...

T cells must adapt to variations in tissue microenvironments; these adaptations include the degree of oxygen availability. The hypoxia-inducible factor (HIF) transcription factors control much of this adaptation, and thus regulate many aspects of T cell activation and function. The HIFs are in turn regulated by oxygen-dependent hydroxylases: both the prolyl hydroxylases (PHDs) which interact with the VHL tumour suppressor and control HIF turnover, and the asparaginyl hydroxylase known as the Factor inhibiting HIF (FIH), which modulates HIF transcriptional activity...

Hypoxia-inducible factor 1 (HIF1) has a crucial function in the regulation of oxygen levels in mammalian cells, especially under hypoxic conditions. Its importance in cardiovascular diseases, particularly in cardiac ischemia, is because of its ability to alleviate cardiac dysfunction. The oxygen-responsive subunit, HIF1α, plays a crucial role in this process, as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival, angiogenesis, and metabolism...

BACKGROUND: Ferroptosis is an iron-dependent and cystathione-non-dependent non-apoptotic cell death characterized by elevated intracellular free iron levels and reduced antioxidant capacity, leading to the accumulation of lipid peroxides. Nuclear receptor coactivator 4 (NCOA4) mediates ferritinophagy, increasing labile iron levels, which can result in oxidative damage. However, the specific mechanism of NCOA4-mediated ferritinophagy in intestinal ischemia-reperfusion and the underlying mechanisms have not been reported in detail...

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50  = 0...

The cotton rose (Hibiscus mutabilis) is a plant species commonly found in tropical and subtropical regions. It is remarkably resilient to waterlogging stress; however, the underlying mechanism behind this trait is yet unknown. This study used hypoxia-tolerant "Danbanhong" (DBH) and more hypoxia-sensitive "Yurui" (YR) genotypes and compared their morpho-physiological and transcriptional responses to hypoxic conditions. Notably, DBH had a higher number of adventitious roots (20.3) compared to YR (10.0), with longer adventitious roots in DBH (18...

Obesity is a chronic disease that affects the energy balance of the whole body. In addition to increasing fat mass, tissue fibrosis occurred in white adipose tissue in obese condition. Fibrosis is the over-activation of fibroblasts leading to excessive accumulation of extracellular matrix, which could be caused by various factors, including the status of adipocytes. The morphology of adipocytes responds rapidly and dynamically to nutrient fluctuations. Adaptive hypertrophy of normal adipocytes protects peripheral organs from damage from lipotoxicity...