Hpgds, or hematopoietic prostaglandin D synthase, is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator, and is involved in the arachidonic acid metabolism pathway [1,2,6,7]. It has significance in various biological processes and diseases, with its study aided by genetic models.

In type 2 diabetic mice, Hpgds deficiency delays normal wound healing, while overexpressing Hpgds in adipose-derived mesenchymal stem cells accelerates diabetic wound healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization, and increasing growth factor production [1]. In A549 cell lines, knockdown of Hpgds promotes lipid synthesis, cell migration, and is more invasive, with the pro-migration effects reversed by ACSL1 knockdown [2]. In small ruminants, miR-665 reduces luteal cell apoptosis via inhibiting Hpgds, which regulates the balance of DP1 and CRTH2 receptors expression [3]. In Ashidan yaks, the copy number variation of Hpgds gene is associated with growth traits, like body weight and body length [4]. In melanoma, T-cell activation abates Hpgds transcription in tumor-associated macrophages, and targeting Hpgds induces anti-tumoral features and sensitizes tumors to αPD1 [5]. In experimental asthma, the Pla2g4c/Ptgs2/Hpgds axis is augmented in bronchial smooth muscle tissues, and increased PGD2 may cause airway hyperresponsiveness [6].

In conclusion, Hpgds plays crucial roles in wound healing, lipid metabolism, luteal cell apoptosis, growth traits, tumor immunity, and airway responsiveness. Gene knockout or knockdown models in mice and cell lines have been instrumental in revealing these functions, providing insights into disease mechanisms such as diabetes-related wound healing issues, lung adenocarcinoma development, and melanoma immunotherapy resistance.