HPGDS

Official Full Name

hematopoietic prostaglandin D synthase

Organism

Homo sapiens

GeneID

27306

Background

Prostaglandin-D synthase is a sigma class glutathione-S-transferase family member. The enzyme catalyzes the conversion of PGH2 to PGD2 and plays a role in the production of prostanoids in the immune system and mast cells. The presence of this enzyme can be used to identify the differentiation stage of human megakaryocytes. [provided by RefSeq, Jul 2008]

Synonyms

GSTS; PGD2; PGDS; GSTS1; GSTS1-1;

Bio Chemical Class

Intramolecular oxidoreductases

Protein Sequence

MPNYKLTYFNMRGRAEIIRYIFAYLDIQYEDHRIEQADWPEIKSTLPFGKIPILEVDGLTLHQSLAIARYLTKNTDLAGNTEMEQCHVDAIVDTLDDFMSCFPWAEKKQDVKEQMFNELLTYNAPHLMQDLDTYLGGREWLIGNSVTWADFYWEICSTTLLVFKPDLLDNHPRLVTLRKKVQAIPAVANWIKRRPQTKL

Open

Disease

Alzheimer disease, Flatworm infection

Approved Drug

1 +

Clinical Trial Drug

1 +

Discontinued Drug

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

Prostaglandin D2 (PGD2) serves as a critical inflammatory lipid mediator synthesized predominantly through the arachidonic acid/cyclooxygenase pathway. Approximately 90% of PGD2 in the body is produced by hematopoietic prostaglandin D synthase (hPGDS), with a smaller amount generated by lipocalin-type prostaglandin D synthase (LPGDS). As a member of the sigma class glutathione-S-transferase family, hPGDS functions as a 23kDa homodimer requiring glutathione and either calcium or magnesium ions as cofactors.

PGD2 exhibits its biological activity by binding to two distinct G protein-coupled receptors: DP1 and DP2 (also known as CRTH2). The DP1 receptor mediates responses such as inhibition of platelet aggregation, vasodilation, and bronchial dilation, whereas the DP2 receptor is primarily associated with pro-inflammatory effects, including immune cell migration, respiratory burst, production of type 2 cytokines, and histamine release.

During different stages of inflammation, PGD2 demonstrates dual regulatory functions. It exerts protective effects in acute inflammatory conditions like dermatitis, colitis, and early-stage endotoxin-induced lung inflammation. However, in chronic allergic inflammation, PGD2 exacerbates leukocyte migration and activation through DP2 receptor engagement, prolonging inflammation duration. Certain PGD2 metabolites, such as 15-deoxy-Δ12,14-PGJ2, also possess anti-inflammatory properties by activating peroxisome proliferator-activated receptor gamma (PPARγ).

Expression of Prostaglandin D2 in Immune Cells

Most of PGD2 originates from mast cells, particularly those residing in organs. Mast cells may produce very little PGD2 when exposed to allergens and IgE receptors cross-link. Mast cells in the lungs generate PGD2 primarily via the COX-1 and hPGDS routes. Those with food allergies have more hPGDS in c-Kit+/FcεRI+ mast cells in their intestinal tissues.

Stimulated eosinophils produce hPGDS and up to 80 pg of PGD2 per 2 million cells. Blood eosinophils from individuals whose lung illness worsens with aspirin have more hPGDS and emit up to 1 ng of PGD2 per 100,000 cells. Basophils also contribute to PGD2 production in IgE-mediated inflammation. Basophils from mouse bone marrow may produce 700 pg of PGD2 for every 500,000 cells when activated.

Specialized antigen-presenting cells, macrophages, and dendritic cells, also produce PGD2. Those with allergic rhinitis have cells in their nasal membrane expressing hPGDS. Macrophages from mouse bone marrow produce 20 ng of PGD2 per million cells when lipopolysaccharide is present. Th2 cells and type 2 innate lymphoid cells (ILC2) also exhibit hPGDS, which regulates allergic inflammation. Cytokine stimulation of ILC2 cells causes them to produce 1.5 ng of PGD2 per 500,000 cells.

Figure 1 illustrates the potential target cells and beneficial effects of hPGDS inhibition in allergic inflammation, highlighting its role in various pathological processes mediated by PGD2. Figure 1. Potential target cells and beneficial effects of hPGDS inhibition in allergic inflammation. (Rittchen S, et al., 2019)

Therapeutic Value of Prostaglandin D2 in Allergic Diseases

Higher levels of PGD2 are connected to worsened symptoms in asthmatics and assist Th2 cells, eosinophils, and basophils migrate and become active via the DP2 receptor. Viral infections in the lungs may increase hPGDS production in bronchial epithelial cells, hence aggravating inflammation. PGD2 also promotes smooth muscle cell development via the DP2 receptor, hence altering the morphology of the airways.

Atopic eczema's PGD2 synthesis is regulated by Langerhans cells and dendritic cells carrying hPGDS. LPGDS may be converted to PGD2 by keratinocytes in the epidermis. Research has shown that hPGDS inhibitors like HQL-79 may reduce the influx of basophils, eosinophils, and lymphocytes into IgE-induced skin inflammation.

Several patents have already been filed for medications blocking hPGDS. Amongst them is ZL-2102. It has begun Phase I clinical trials to determine its safety and mechanism of action in diseases like asthma and chronic obstructive lung disease. Another hPGDS inhibitor, TAS-205, has been well tolerated in Phase I trials with Duchenne muscular dystrophy patients. More research is required, however, to determine the optimal moment to begin medication and how to group patients as PGD2 serves various functions at various phases of inflammation. Should inhibiting PGD2 synthesis assist regulate allergic inflammation better than DP2 receptor blockers, additional study is required to be certain.

References:

Kanaoka Y, Urade Y. Hematopoietic prostaglandin D synthase. Prostaglandins Leukot Essent Fatty Acids. 2003;69(2-3):163-167. doi:10.1016/s0952-3278(03)00077-2.
Rittchen S, Heinemann A. Therapeutic Potential of Hematopoietic Prostaglandin D₂ Synthase in Allergic Inflammation. Cells. 2019 Jun 20;8(6):619.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry