Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Reproductive Genomics Program, The Fertility Center, Grand Rapids, MI, USA.
Reprod Sci. 2022 Nov;29(11):3055-3077. doi: 10.1007/s43032-021-00726-9. Epub 2021 Sep 13.
Intraperitoneal adhesions complicate over half of abdominal-pelvic surgeries with immediate, short, and long-term sequelae of major healthcare concern. The pathogenesis of adhesion development is similar to the pathogenesis of wound healing in all tissues, which if unchecked result in production of fibrotic conditions. Given the similarities, we explore the published literature to highlight the similarities in the pathogenesis of intra-abdominal adhesion development (IPAD) and other fibrotic diseases such as keloids, endometriosis, uterine fibroids, bronchopulmonary dysplasia, and pulmonary, intraperitoneal, and retroperitoneal fibrosis. Following a literature search using PubMed database for all relevant English language articles up to November 2020, we reviewed relevant articles addressing the genetic and epidemiological similarities and differences in the pathogenesis and pathobiology of fibrotic diseases. We found genetic and epidemiological similarities and differences between the pathobiology of postoperative IPAD and other diseases that involve altered fibroblast-derived cells. We also found several genes and single nucleotide polymorphisms that are up- or downregulated and whose products directly or indirectly increase the propensity for postoperative adhesion development and other fibrotic diseases. An understanding of the similarities in pathophysiology of adhesion development and other fibrotic diseases contributes to a greater understanding of IPAD and these disease processes. At a very fundamental level, blocking changes in the expression or function of genes necessary for the transformation of normal to altered fibroblasts may curtail adhesion formation and other fibrotic disease since this is a prerequisite for their development. Similarly, applying measures to induce apoptosis of altered fibroblast may do the same; however, apoptosis should be at a desired level to simultaneously ameliorate development of fibrotic diseases while allowing for normal healing. Scientists may use such information to develop pharmacologic interventions for those most at risk for developing these fibrotic conditions.
腹腔内粘连是影响超过一半的腹部-盆腔手术的主要并发症，具有即时、短期和长期的重大医疗后果。粘连形成的发病机制与所有组织的创伤愈合发病机制相似，如果不加控制，会导致纤维性疾病的产生。鉴于其相似性，我们探讨了已发表的文献，以强调腹腔内粘连形成（IPAD）与其他纤维性疾病（如瘢痕疙瘩、子宫内膜异位症、子宫肌瘤、支气管肺发育不良以及肺、腹腔和腹膜后纤维化）的发病机制相似之处。通过使用 PubMed 数据库对截至 2020 年 11 月的所有相关英文文献进行文献检索，我们复习了相关文章，以探讨纤维性疾病发病机制和病理生物学方面的遗传和流行病学相似性和差异性。我们发现，术后 IPAD 的病理生物学与涉及改变的成纤维细胞衍生细胞的其他疾病之间存在遗传和流行病学的相似性和差异性。我们还发现了几个基因和单核苷酸多态性，它们的表达上调或下调，其产物直接或间接地增加了术后粘连形成和其他纤维性疾病的易发性。了解粘连形成和其他纤维性疾病的病理生理学相似性有助于更好地理解 IPAD 和这些疾病过程。在非常基础的层面上，阻断正常成纤维细胞向改变的成纤维细胞转化所需的基因表达或功能的改变，可能会抑制粘连形成和其他纤维性疾病的发生，因为这是它们发展的前提。同样，应用措施诱导改变的成纤维细胞凋亡也可能会产生同样的效果；然而，凋亡应该处于期望的水平，以同时改善纤维性疾病的发展，同时允许正常愈合。科学家们可能会利用这些信息来开发针对这些纤维性疾病风险最高的人群的药物干预措施。
