Abstract

Background Postoperative abdominal adhesion remains one of the frequent complications after abdominal surgery and lacks effective intervention. Peritoneal mesothelial cell injury and healing play crucial roles in the process of adhesion formation, and identifying this mechanism might provide new insight into possible new therapeutic strategies for this disease. Transmembrane and immunoglobulin domain-containing 1 (TMIGD1) has been proven to protect renal epithelial cells from injury induced by oxidative stress and has also been identified as a novel adhesion molecule. Here, we investigated the role of TMIGD1 and its possible mechanism in adhesion formation. Materials and Methods Immunohistochemistry (IHC), qPCR, and immunofluorescence (IHF) were used to detect the expression of TMIGD1. The grade and tenacity score of adhesion were used to evaluate the adhesion formation conditions. A TMIGD1-overexpressing HMrSV5 cell line was established. MTT assay, Western blotting, Annexin V apoptosis analysis, and CK19 staining were used to measure mesothelial cell viability, apoptosis, and completeness. ROS and MDA detection were used to measure mesothelial cell oxidative stress levels. JC-1 staining, IHF, and transmission electron microscopy were performed to assess mitochondrial function. Scratch-wound and adhesion assays were used to evaluate the adhesion ability of mesothelial cells. Results First, we showed that TMIGD1 was decreased in mouse abdominal adhesion tissue and peritoneal mesothelial cells. Second, TMIGD1 overexpression inhibited adhesion formation. Third, TMIGD1 overexpression protected mesothelial cells from hydrogen peroxide- (H2O2-) induced oxidative stress injury. Fourth, TMIGD1 overexpression alleviated oxidative stress by protecting the mitochondrial function of mesothelial cells. In addition, TMIGD1 overexpression enhanced mesothelial cell adhesion. Conclusion Our findings suggest that TMIGD1 protects mesothelial cells from oxidative stress injury by protecting their mitochondrial function, which is decreased in regular abdominal adhesion tissue. In addition, TMIGD1 enhances peritoneal mesothelial cell adhesion to promote healing.

Highlights

  • Postoperative abdominal adhesion remains one of the frequent complications after abdominal surgery and lacks effective intervention

  • We discovered that Transmembrane and immunoglobulin domain-containing 1 (TMIGD1) expression is decreased in abdominal adhesion tissue compared to normal peritoneum at postoperative day (POD) 3 through analyzing the microarray data from the GSE4715 dataset in GEO (gene 2R software; adhesion tissue vs. normal peritoneum; screening criteria: ∣LogFC ∣ >1 and P < 0:05; https://www.ncbi.nlm.nih .gov/geo/, Figures 1(a) and 1(b))

  • To validate this finding further, we measured TMIGD1 expression in mouse abdominal adhesion tissues via IHC. These analyses indicated that TMIGD1 expression is decreased in adhesion tissue compared to normal peritoneum at POD 3 and POD 10 (Figures 2(a) and 2(b)). q-PCR assays revealed the same molecular alteration in adhesion tissue (Figure 2(c))

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Summary

Introduction

Postoperative abdominal adhesion remains one of the frequent complications after abdominal surgery and lacks effective intervention. Peritoneal mesothelial cell injury and healing play crucial roles in the process of adhesion formation, and identifying this mechanism might provide new insight into possible new therapeutic strategies for this disease. TMIGD1 overexpression protected mesothelial cells from hydrogen peroxide- (H2O2-) induced oxidative stress injury. TMIGD1 overexpression alleviated oxidative stress by protecting the mitochondrial function of mesothelial cells. Our findings suggest that TMIGD1 protects mesothelial cells from oxidative stress injury by protecting their mitochondrial function, which is decreased in regular abdominal adhesion tissue. There is no effective management strategy for postoperative abdominal adhesion other than enterolysis, which is an invasive method with a high probability of reinjury and readhesion [3]. Mesothelial cell plays a critical role in the process of peritoneal tissue healing and adhesion formation.

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Conclusion

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