Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, P.R. China.
Int J Mol Med. 2019 Nov;44(5):1609-1618. doi: 10.3892/ijmm.2019.4329. Epub 2019 Sep 2.
Parastomal hernia (PH) is a common complication following stoma formation. Abnormal collagen synthesis has been suggested to be involved in PH. The aim of the present study is to explore the effect and mechanism of the collagen synthesis on PH. Data from 157 patients with rectal cancer who received permanent colostomy were retrospectively collected and analyzed to identify the risk factors for PH. Primary culture of skin fibroblasts from patients with or without PH were performed. Cell viability, migration and invasion levels were detected by Cell Counting Kit‑8, and wound healing and Transwell assays, respectively. Reverse transcription quantitative polymerase chain reaction and western blot analysis assays were performed to measure the gene and protein expression levels, respectively. The risk factors of sex, body mass index, aperture size and collagen expression were closely associated with the occurrence of PH. α1 (III) procollagen expression levels were significantly increased in patients with PH, while no marked difference in α1 (I) procollagen mRNA expression levels were observed in patients with or without PH. The viability and motility of fibroblasts from the patients with hernia were suppressed. The expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9 were decreased while the levels of collagen III and metalloproteinase inhibitor 1 (TIMP‑1) were increased in the fibroblasts from the patients with PH. Silencing TIMP‑1 expression promoted fibroblast migration and invasion and reversed the patterns of MMP‑2, MMP‑9 and collagen III expression in fibroblasts from the patients with PH. Decreased collagen III may inhibit the development of PH, potentially through decreases in TIMP‑1 expression. Therefore, the results from the present study may provide a novel target for PH therapy.
肠造口术后疝（PH）是造口术后的常见并发症。异常的胶原合成被认为与 PH 有关。本研究旨在探讨胶原合成对 PH 的影响和作用机制。回顾性收集并分析了 157 例接受永久性结肠造口术的直肠癌患者的数据，以确定 PH 的危险因素。对有或无 PH 的患者进行皮肤成纤维细胞的原代培养。通过细胞计数试剂盒-8 检测细胞活力、迁移和侵袭水平，通过划痕愈合和 Transwell 测定分别检测细胞迁移和侵袭水平。通过逆转录定量聚合酶链反应和 Western blot 分析检测基因和蛋白表达水平。性别、体重指数、孔径大小和胶原表达的危险因素与 PH 的发生密切相关。PH 患者的α1（III）前胶原表达水平显著升高，而 PH 患者和无 PH 患者的α1（I）前胶原 mRNA 表达水平无明显差异。疝患者的成纤维细胞活力和迁移能力受到抑制。PH 患者成纤维细胞中基质金属蛋白酶（MMP）-2 和 MMP-9 的表达水平降低，而胶原 III 和金属蛋白酶抑制剂 1（TIMP-1）的表达水平升高。沉默 TIMP-1 表达促进了 PH 患者成纤维细胞的迁移和侵袭，并逆转了 PH 患者成纤维细胞中 MMP-2、MMP-9 和胶原 III 的表达模式。胶原 III 的减少可能通过降低 TIMP-1 的表达来抑制 PH 的发展。因此，本研究的结果可为 PH 治疗提供新的靶点。
