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IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2025-04-01 DOI:10.1186/s10020-025-01167-9

Hilal Sengul, Vasiliki Bantavi, Laura Gloeck, Andrew Y F Li Yim, Patrick Leven, Patrik Efferz, Bianca Schneiker, Mariola Lysson, Wouter J De Jonge, Sven Wehner

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引用次数: 0

摘要

背景：结肠吻合口漏（CAL）是结肠吻合口愈合障碍（CAH）引起的术后并发症。伤口愈合包括几个协调良好的阶段，目前尚未对 CAH 或 CAL 进行全面研究。本研究旨在提供吻合口组织不同肠层在不同愈合阶段的转录谱，并确定与 CAL 相关的基因：方法：用 8 根间断缝合线为小鼠构建近端结肠吻合口。方法：用 8 根间断缝合线为小鼠构建近端结肠吻合口，分别在术后 6 小时、24 小时和 72 小时评估吻合口并发症。通过3'bulk mRNA测序分析了吻合口内层（粘膜和粘膜下层）和外层（外侧肌层）以及正常对照组组织的转录谱，以确定各层特异性愈合和渗漏途径。对 CAL 和 CAH 之间不同的选择性靶基因进行了蛋白质表达测定：结果：我们的数据表明，在 CAH 期间，粘膜/粘膜下层和外层肌分别于 6 小时、24 小时和 72 小时进入炎症期、增殖期和组织重塑期。我们观察到，CAH 和 CAL 的粘膜/粘膜下层的转录谱不同，但外部肌层的转录谱不同。特别是，与细胞外重塑（包括 Col18a1 和 Col16a1）和伤口愈合（Pdpn 和 Timp1）相关的基因在 CAL 组织的粘膜/粘膜下层的表达量低于 CAH。同样，与 CAH 组织相比，CAL 组织中胶原蛋白和 IL-34 蛋白水平降低，而 TGF-β 伪受体 BAMBI 水平升高：结论：在CAH的炎症、增殖和细胞外重塑阶段，粘膜/粘膜下层和肌层大多处于同步状态。CAH和CAL的吻合口粘膜/粘膜下与细胞外重塑和伤口愈合相关的基因转录谱不同，表明这些通路的基因可能对CAL有影响。

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Layer-specific molecular signatures of colon anastomotic healing and leakage in mice.

Background: Colon anastomotic leakage (CAL) is a postoperative complication originating from disturbed colon anastomotic healing (CAH). Wound healing involves several well-coordinated stages, which have not been comprehensively studied for CAH or CAL. This study aims to provide transcriptional profiles of different intestinal layers of anastomotic tissues throughout distinct healing stages and to identify CAL-related genes.

Methods: Proximal colon anastomosis was constructed with 8 interrupted sutures in mice. Six hours, 24 h and 72 h after surgery, anastomotic complications were assessed. Transcriptional profiles of inner (mucosa and submucosa) and outer (muscularis externa) layer of the anastomotic and naive control tissues were analyzed with 3' bulk mRNA sequencing to identify the layer-specific healing and leakage pathways. Selective target genes differing between CAL and CAH were measured for their protein expression.

Results: Our data indicate that the mucosa/submucosa and muscularis externa enter inflammation stage at 6 h, proliferation stage at 24 h and tissue remodeling stage at 72 h during CAH. We observed that transcription profiles of the mucosa/submucosa, but not the muscularis externa, differ between CAH and CAL. Particularly, genes related to extracellular remodeling (including Col18a1 and Col16a1) and wound healing (Pdpn and Timp1) showed lower expression in the mucosa/submucosa of CAL tissue compared to CAH. Conformingly, protein levels for collagens as well IL-34 were decreased in CAL, while the TGF-β-pseudo-receptor BAMBI was increased in CAL compared to CAH tissues.

Conclusions: Mucosa/submucosa and muscularis externa are mostly in synchronization during the inflammation, proliferation, and extracellular remodeling stages during CAH. Transcriptional profiles within the anastomotic mucosa/submucosa differ between CAH and CAL in genes related to extracellular modelling and wound healing, indicating that genes of these pathways may contribute to CAL.

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.