Recent advances in studies of 15-PGDH as a key enzyme for the degradation of prostaglandins

生物 癌症研究 抑制器 脱氢酶 癌症 细胞生物学 生物化学 遗传学
作者
Chen‐Chen Sun,Zuoqiong Zhou,Dong Kwon Yang,Zhanglin Chen,Yunyi Zhou,Wei Wen,Feng Chen,Lan Zheng,Xiyang Peng,Changfa Tang
出处
期刊:International Immunopharmacology [Elsevier BV]
卷期号:101 (Pt B): 108176-108176 被引量:39
标识
DOI:10.1016/j.intimp.2021.108176
摘要

15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) is ubiquitously expressed in mammalian tissues and catalyzes the degradation of prostaglandins (PGs; mainly PGE2, PGD2, and PGF2α) in a process mediated by solute carrier organic anion transport protein family member 2A1 (SLCO2A1; also known as PGT, OATP2A1, PHOAR2, or SLC21A2). As a key enzyme, 15-PGDH catalyzes the rapid oxidation of 15-hydroxy-PGs into 15-keto-PGs with lower biological activity. Increasing evidence suggests that 15-PGDH plays a key role in many physiological and pathological processes in mammals and is considered a potential pharmacological target for preventing organ damage, promoting bone marrow graft recovery, and enhancing tissue regeneration. Additionally, results of whole-exome analyses suggest that recessive inheritance of an HPGD mutation is associated with idiopathic hypertrophic osteoarthropathy. Interestingly, as a tumor suppressor, 15-PGDH inhibits proliferation and induces the differentiation of cancer cells (including those associated with colorectal, lung, and breast cancers). Furthermore, a recent study identified 15-PGDH as a marker of aging tissue and a potential novel therapeutic target for resisting the complex pathology of aging-associated diseases. Here, we review and summarise recent information on the molecular functions of 15-PGDH and discuss its pathophysiological implications.
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