Differential Gene Expression in Normal and Abnormal Tracheal Wound Healing
Joanna Weber1, Mirza Zain Baig1, Zaid Muslim1, Al Haitham Al Shetawi2, Cliff Connery2, Faiz Bhora1.
1Nuvance Health, Danbury, CT, USA, 2Nuvance Health, Poughkeepsie, NY, USA.
OBJECTIVE: Compared to other tissues, there has been little focus on wound healing of the trachea. This study expands on our previous experiments in tracheal bioengineering to attempt to identify possible mechanisms responsible for abnormal tracheal wound healing. METHODS: A secondary analysis of paraffin-embedded samples from previous experiments of porcine orthotopic tracheal graft transplantation was performed. Gene expression with an array of genes from known wound healing pathways was measured by isolating RNA from the formalin-fixed paraffin-embedded samples. Differential expression was computed by normalizing to expression of healthy tracheal tissue. RESULTS: Figure 1 shows the differential expression of genes correlated to animal survival time. Differences were observed between animals who survived to the study end (~90 days) and those that suffered from stenosis due to abnormal healing and granulation tissue formation at the site of anastomosis (20-40 days). EGFR, TGFB3, COL14A1, DCN, ITGB5, and TGFBR3 expression was increased in 90-day animals but decreased in animals with stenosis. SMAD3, ACTA2, AKT1, FGF2, CTGF, RAC1, and RPL13A expression was similar to control in 90-day animals but downregulated in animals with stenosis. These results suggest that specific components of the extracellular matrix (DCN, COL14A1, TGFBR3) modulate EGF and TGFB signaling pathways to promote wound resolution, limit granulation tissue growth, and return to a healthy state. CONCLUSIONS: We have identified differences in gene expression between normal and abnormal healing that suggest several pathways necessary for normal wound resolution. Future work will explore causal pathways to identify potential upstream molecular targets and new therapeutic options.
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