Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 15, Issue 13, Pages 2783-2797Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.35128
Keywords
COX-2; PGE(2); endometriosis; pain; estrogen
Categories
Funding
- National Natural Science Foundation of China (NSFC) [31970798, 91542108, 81471513, 31671200, 81571509]
- Shanghai Rising-Star Program [16QA1400800]
- Innovation-oriented Science and Technology Grant from NPFPC Key Laboratory of Reproduction Regulation [CX2017-2]
- Program for Zhuoxue of Fudan University
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Endometriosis (EMS) is the most common gynecological disease in women of reproductive age, and it is associated with chronic pelvic pain, dyspareunia and infertility. As a consequence of genetic, immune and environmental factors, endometriotic lesions have high cyclooxygenase (COX)-2 and COX-2-derived prostaglandin E-2 (PGE(2)) biosynthesis compared with the normal endometrium. The transcription of the PTGS2 gene for COX-2 is associated with multiple intracellular signals, which converge to cause the activation of mitogen-activated protein kinases (MAPKs). COX-2 expression can be regulated by several factors, such as estrogen, hypoxia, proinflammatory cytokines, environmental pollutants, metabolites and metabolic enzymes, and platelets. High concentrations of COX-2 lead to high cell proliferation, a low level of apoptosis, high invasion, angiogenesis, EMS-related pain and infertility. COX-2-derived PGE(2) performs a crucial function in EMS development by binding to EP2 and EP4 receptors. These basic findings have contributed to COX-2-targeted treatment in EMS, including COX-2 inhibitors, hormone drugs and glycyrrhizin. In this review, we summarize the most recent basic research in detail and provide a short summary of COX-2-targeted treatment.
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