Ferreira J P S, Kuang M, Parente M P L, Natal Jorge R M, Wang R, Eppell S J, Damaser M
Department of Mechanical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal; Institute of Science and Innovation in Mechanical and Industrial Engineering, Porto, Portugal; Department of Biomedical Engineering, Lerner Research Institute and Glickman Urological Institute, Cleveland Clinic Foundation, OH, USA.
Department of Biomedical Engineering, Lerner Research Institute and Glickman Urological Institute, Cleveland Clinic Foundation, OH, USA.
Acta Biomater. 2020 Jul 1;110:175-187. doi: 10.1016/j.actbio.2020.03.046. Epub 2020 Apr 24.
The remodeling mechanisms that cause connective tissue of the vaginal wall, consisting mostly of smooth muscle, to weaken after vaginal delivery are not fully understood. Abnormal remodeling after delivery can contribute to development of pelvic organ prolapse and other pelvic floor disorders. The present study used vaginal smooth muscle cells (vSMCs) isolated from knockout mice lacking the expression of the lysyl oxidase-like1 (LOXL1) enzyme, a well-characterized animal model for pelvic organ prolapse. We tested if vaginal smooth muscle cells from LOXL1 knockout mice have altered mechanics including stiffness and surface adhesion. Using atomic force microscopy, we performed nanoindentations on both isolated and confluent cells to evaluate the effect of LOXL1 knockout on in vitro cultures of vSMCs cells from nulliparous mice. The results show that LOXL1 knockout vSMCs have increased stiffness in pre-confluent but decreased stiffness in confluent cultures (p* < 0.05) and significant decreased surface adhesion in pre-confluent cultures (p* < 0.05). This study provides evidence that the weakening of vaginal connective tissue in the absense of LOXL1 changes the mechanical properties of the vSMCs. STATEMENT OF SIGNIFICANCE: Pelvic organ prolapse is a common condition affecting millions of women worldwide, which significantly impacts their quality of life. Alterations in vaginal and pelvic floor mechanical properties can change their ability to support the pelvic organs. This study provides evidence of altered stiffness of vaginal smooth muscle cells from mice resembling pelvic organ prolapse. The results from this study set a foundation to develop pathophysiology-driven therapies focused on the interplay between smooth muscle mechanics and extracellular matrix remodeling.
导致主要由平滑肌组成的阴道壁结缔组织在阴道分娩后减弱的重塑机制尚未完全了解。分娩后的异常重塑会导致盆腔器官脱垂和其他盆底疾病的发生。本研究使用了从缺乏赖氨酰氧化酶样1（LOXL1）酶表达的基因敲除小鼠中分离出的阴道平滑肌细胞（vSMC），这是一种用于研究盆腔器官脱垂的特征明确的动物模型。我们测试了来自LOXL1基因敲除小鼠的阴道平滑肌细胞的力学特性是否发生改变，包括硬度和表面粘附性。使用原子力显微镜，我们对分离的和汇合的细胞进行了纳米压痕试验，以评估LOXL1基因敲除对未生育小鼠vSMC细胞体外培养的影响。结果表明，LOXL1基因敲除的vSMC在汇合前硬度增加，但在汇合培养时硬度降低（p*<0.05），并且在汇合前培养时表面粘附性显著降低（p*<0.05）。本研究提供了证据，表明在缺乏LOXL1的情况下阴道结缔组织的减弱会改变vSMC的力学特性。重要性声明：盆腔器官脱垂是一种影响全球数百万女性的常见疾病，严重影响她们的生活质量。阴道和盆底力学特性的改变会影响它们支撑盆腔器官的能力。本研究提供了类似于盆腔器官脱垂的小鼠阴道平滑肌细胞硬度改变的证据。本研究结果为开发以病理生理学为驱动的治疗方法奠定了基础，该方法侧重于平滑肌力学与细胞外基质重塑之间的相互作用。
