Alpha-1-antitrypsin improves anastomotic healing in intestinal epithelial cells model
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In brief
In brief
This in vitro study demonstrates that alpha-1-antitrypsin (AAT) at physiological concentrations significantly accelerates intestinal epithelial cell wound closure and proliferation, suggesting potential therapeutic application for preventing anastomotic leakage in pediatric intestinal surgery.
- Alpha-1-antitrypsin (AAT) at physiological concentrations (1 mg/ml) accelerates intestinal epithelial wound closure by 2-fold compared to controls.
- AAT treatment significantly increases expression of proliferation genes (CDKN1A, CDKN2A, WNT3, COL3A1) in intestinal epithelial cells.
- Local AAT administration shows therapeutic potential to reduce anastomotic leak risk in pediatric intestinal surgery.
- AAT decreases IL-8 levels without affecting CXCL8 mRNA, suggesting anti-inflammatory effects during wound healing.
- In vitro model demonstrates 97% wound closure at 18 hours with AAT versus 60% in controls, supporting clinical translation studies.
Written by the GCMD Library team from the article.
Abstract
Purpose
Intestinal anastomosis is a routine procedure in pediatric surgery, with leakage being a significant complication. Human alpha1-antitrypsin (AAT), whose physiological serum concentrations range from 0.9–2.0 mg/ml, is known to accelerate wound healing and stimulate the expression of cell proliferation-related genes. We hypothesized that AAT might enhance anastomotic healing.
Methods
In a monolayer of non-tumorigenic HIEC-6 epithelial cells derived from fetal intestine a scratch was created. Standard medium without (control) or with AAT (0.5 and 1 mg/ml) was added. Cells were observed using a Life-Cell Imaging System. Cell proliferation was assessed, and the expression of proliferation-related genes was measured by qRT-PCR.
Results
In the presence of AAT, the scratch closed significantly faster. Cells treated with 1 mg/ml AAT showed 53% repopulation after 8 h and 97% after 18 h, while control cells showed 24% and 60% repopulation, respectively (p < 0.02). The treatment with AAT induced HIEC-6-cell proliferation and significantly increased the mRNA-expression of CDKN1A, CDKN2A, ANGPTL4, WNT3 and COL3A1 genes. AAT did not change the mRNA-expression of CXCL8 but decreased levels of IL-8 as compared to controls.
Conclusion
At physiological concentrations AAT accelerates the confluence of intestinal cells and increases cell proliferation. The local administration of AAT may bear therapeutic potential to improve anastomotic healing.