2023-08-09 バッファロー大学(UB)
◆研究では、神経と痛みの関係を探り、神経栄養因子の過剰な発現が痛みと関連することを明らかにした。この知見により、新しい治療法の標的が提案され、子宮内膜症の痛みの薬理学的アプローチが期待されている。
<関連情報>
- https://www.buffalo.edu/news/releases/2023/08/Endometriosis-UB-research-new-targets.html
- https://www.sciencedirect.com/science/article/pii/S0002944023001645?via%3Dihub
子宮内膜症における骨盤痛の新規治療標的であるニューロトロフィンとその受容体は、JNKシグナル伝達経路を介してIL-1βによって協調的に制御される。
Neurotrophins and Their Receptors, Novel Therapeutic Targets for Pelvic Pain in Endometriosis, Are Coordinately Regulated by IL-1β via the JNK Signaling Pathway
Jie Yu, Sarah L. Berga, Eric Zou, Andrew D. Schrepf, Daniel J. Clauw, Sawsan As-Sanie, Robert N. Taylor
American Journal of Pathology Available online :8 May 2023
DOI:https://doi.org/10.1016/j.ajpath.2023.04.007
Pelvic pain in women with endometriosis is attributed to neuroinflammation and afferent nociceptor nerves in ectopic and eutopic endometrium. The hypothesis that uterine nociception is activated by IL-1β, a prominent cytokine in endometriosis, was tested herein. Immunofluorescence histochemistry confirmed the presence of neurons in human endometrial tissue. Expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors in endometrial tissue and cells was validated by immunohistochemistry and Western blotting. Isolated endometrial stromal cells (ESCs) were subjected to dose-response and time-course experiments with IL-1β and kinase inhibitors to characterize in vitro biomarkers. Neural biomarkers were co-localized in endometrial nerve fibers. NGF, BDNF, and their receptors tropomyosin receptor kinase (Trk) A, TrkB, and p75 neurotrophin receptor were all expressed in primary ESCs. IL-1β stimulated higher TrkA/B expression in ESCs derived from endometriosis cases (2.8- ± 0.2-fold) than cells from controls (1.5- ± 0.3-fold, t-test, P < 0.01), effects that were mediated via the c-Jun N-terminal kinase (JNK) pathway. BDNF concentrations trended higher in peritoneal fluid of endometriosis cases but were not statistically different from controls (P = 0.16). The results support the hypothesis that NGF and BDNF and their corresponding receptors orchestrate innervation of the endometrium, which is augmented by IL-1β. We postulate that JNK inhibitors, such as SP600125, have the potential to reduce neuroinflammation in women with endometriosis.
