Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis

Scientific Reports
Dingmin YanSun-Wei Guo

Abstract

Endometriotic lesions are known to be hyperinnervated, especially in lesions of deep endometriosis (DE), which are frequently in close proximity to various nerve plexuses. DE lesions typically have higher fibromuscular content than that of ovarian endometriomas (OE) lesions, but the underlying reason remains elusive. Aside from their traditional role of pain transduction, however, whether or not sensory nerves play any role in the development of endometriosis is unclear. Here, we show that, thorough their respective receptors neurokinin receptor 1 (NK1R), calcitonin receptor like receptor (CRLR), and receptor activity modifying protein 1 (RAMP-1), neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT) and further turn stromal cells into smooth muscle cells (SMCs) in endometriotic lesions, resulting ultimately in fibrosis. We show that SP and CGRP, or the rat dorsal root ganglia (DRG) supernatant, through the induction of NK1R and CGRP/CRLR/RAMP-1 signaling pathways, promoted EMT, FMT and SMM in endometriosis, resulting in increased migratory and invasive propensity, cell contractility, production of collagen...Continue Reading

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Citations

Apr 14, 2020·The Journal of Clinical Endocrinology and Metabolism·Ding DingSun-Wei Guo
Apr 26, 2020·Reproductive Sciences·Ding DingSun-Wei Guo
Nov 18, 2020·International Journal of Molecular Sciences·Carla Trapero, Mireia Martín-Satué
Feb 20, 2021·Reproductive Biology and Endocrinology : RB&E·Xiaofang XuSun-Wei Guo
Jul 11, 2020·Best Practice & Research. Clinical Obstetrics & Gynaecology·Paul J YongMichael S Anglesio
Aug 20, 2020·The Journal of Clinical Endocrinology and Metabolism·Dingmin YanSun-Wei Guo
May 3, 2021·Annals of Clinical and Translational Neurology·Bianca RaffaelliUwe Reuter
May 29, 2021·Cell·Philippa T K Saunders, Andrew W Horne
Feb 1, 2022·Reproductive Sciences·Shenghui HuangTingting Zhang

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