Analysis of HIF-1 Signaling Pathway in Ischemic Stroke

Ischemic stroke is caused by inadequate blood and oxygen supply to the cerebral vessels. Most cellular responses to hypoxia are associated with a family of transcription factors called hypoxia-inducible factors (HIF), which induce the expression of a variety of glycolysis-related genes, thereby helping cells and tissues to adapt to hypoxia. HIF-1 is composed of two subunits: HIF-1α and HIF-1β. During stroke, HIF-1α serves as a sensitive regulator of oxygen homeostasis. Its expression is rapidly induced after hypoxia/ischemia and participates in the pathology of stroke by regulating glucose metabolism, angiogenesis, erythropoiesis, cell survival, and other pathways. process. Furthermore, the spatiotemporal expression profile of HIF-1α in the brain changes with the progression of ischemic stroke. Based on its role in stroke, HIF-1 is expected to be a potential target for stroke therapy.

Fig. 1. HIF1: regulatory mechanisms and drug development in stroke. (Pan et al., 2021)

Our Analysis Services of HIF-1 Signaling Pathway in Ischemic Stroke

Ace Therapeutics provides reliable services to analyze the role and regulatory mechanisms of HIF-1 in stroke. Utilizing state-of-the-art technologies and methodologies, our team of experienced researchers and experts aims to discover targeted downstream genes for HIF and provide new strategies for stroke treatment.

We utilize established in vitro and in vivo models of ischemic stroke to analyze the regulatory mechanisms of HIF-1α and its various roles in ischemic stroke, particularly in the four major cell types of the neurovascular unit (NVU) (i.e., neurons, astrocytes, endothelial cells, and microglia). We focus on the expression of HIF in different stages/types of stroke

• Neurogenesis: Wnt, β-catenin
• Early stroke: Acyl CoA synthase long chain family member 4 (ACSL4)
• Middle and later stage of stroke: NLR family containing pyrin domain protein 3 (NLRP3), interleukin 18 (IL-18), caspase-1, interleukin 1β (IL-1β)
• Transient focal cerebral ischemia: Erythropoietin (EPO), vascular endothelial growth factor (VEGF), caspase-3, caspase-9
• Ischemia reperfusion: Bcl-2 family proteins with BH3 domain (NIX), BCL2/viral E1β counterpart protein 3 (BNIP3)

Cerebral Ischemia Intervention R&D Services Targeting HIF-1α

Our experts can help clients develop new interventions for cerebral ischemia that act on the HIF-1α target, thus providing novel suggestions for the treatment of ischemic stroke.

• Biological factors. We can help clients develop a variety of endogenous factors to modulate HIF-1α, such as neurotransmitters, amino acids, and inorganic salts.
• Non-coding RNAs (miRNAs). We can help clients develop several miRNAs, including miR-376b-5p, miR-433, miR-335, miRNA-210, and miR-155-5p, to regulate HIF-1α during cerebral ischemia.
• Natural compounds. We can help clients develop natural compounds, chemical and herbal compounds that can reduce cerebral ischemic injury through HIF-1α.

Ace Therapeutics provides comprehensive analysis services to elucidate biological functions and regulatory mechanisms of HIF-1 in ischemic stroke. Through advanced methodologies and partnerships, we help our clients develop HIF as a new potential target for the treatment of stroke. If you are interested in our services, please do not hesitate to contact us!

1. Pan, Z., et al. (2021). Hypoxia-inducible factor-1: Regulatory mechanisms and drug development in stroke. Pharmacological Research, 170, 105742.