Amaral Ana, Fernandes Carina, Szóstek-Mioduchowska Anna, Lukasik Karolina, Rebordão Maria Rosa, Pinto-Bravo Pedro, Skarzynski Dariusz Jan, Ferreira-Dias Graça
CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
Life (Basel). 2021 Oct 19;11(10):1107. doi: 10.3390/life11101107.
Cathepsin G (CAT) is a protease released by neutrophils when forming neutrophil extracellular traps that was already associated with inducing type I collagen (COL1) in equine endometrium in vitro. Endometrosis is a fibrotic condition mainly characterized by COL1 deposition in the equine endometrium. The objective was to evaluate if noscapine (an alkaloid for cough treatment with anti-neoplastic and anti-fibrotic properties) would reduce transcription (evaluated by qPCR) and COL1 protein relative abundance (evaluated by western blot) induced by CAT in equine endometrial explants from follicular and mid-luteal phases treated for 24 or 48 h. The explants treated with CAT increased COL1 expression. Noscapine decreased transcription at both estrous cycle phases, but COL1 relative protein only at the follicular phase, both induced by CAT. Additionally, the noscapine anti-fibrotic action was found to be more effective in the follicular phase. The CAT treatment caused more fibrosis at the longest period of treatment, while noscapine acted better at the shortest time of treatment. Our results showed that noscapine could act as an anti-fibrotic drug in equine endometrosis by inhibiting CAT in vitro. Noscapine offers a new promising therapeutic tool for treating fibrosis as a single non-selective agent to be considered in the future.
组织蛋白酶G(CAT)是中性粒细胞在形成中性粒细胞胞外陷阱时释放的一种蛋白酶,体外实验中已发现它与马子宫内膜中I型胶原蛋白(COL1)的诱导有关。子宫内膜纤维化是一种纤维化病症,主要特征是马子宫内膜中COL1沉积。本研究旨在评估那可丁(一种具有抗肿瘤和抗纤维化特性的止咳生物碱)是否会降低经24小时或48小时处理的卵泡期和黄体中期马子宫内膜外植体中由CAT诱导的转录(通过qPCR评估)和COL1蛋白相对丰度(通过蛋白质印迹评估)。用CAT处理的外植体COL1表达增加。那可丁在两个发情周期阶段均降低转录,但仅在卵泡期降低由CAT诱导的COL1相对蛋白水平。此外,发现那可丁的抗纤维化作用在卵泡期更有效。CAT处理在最长治疗期导致更多纤维化,而那可丁在最短治疗时间效果更佳。我们的结果表明,那可丁在体外可通过抑制CAT作为马子宫内膜纤维化的抗纤维化药物。那可丁作为一种单一的非选择性药物,为未来治疗纤维化提供了一种新的有前景的治疗工具。