FIGURE 6.

The over-expression of Sox18 preserves lung mechanics in mice exposed to high tidal mechanical ventilation. Mice were injected or not with pCMV6-SOX18 (SOX18) or control pDST-luciferase plasmids using in vivo-jetPEI® via the tail vein. After 64 h, the mice were exposed or not to ventilation with high tidal volumes (HTV; 30 ml/kg, 75 bpm, 0.5 FiO2) for 8 h. HLMVECs were treated with AdSOX18 for 48 h to overexpress SOX18 and subjected to cyclic stretch for 8h. Immunoblot analysis demonstrated a significant increase in Sox18 protein levels in the lungs of mice given the pCMV6-SOX18 plasmid (A). The analysis of dynamic pressure-volume relationships in the mouse lung indicated that HTV ventilation caused a loss of Optimal Respiratory System Compliance (B) and Respiratory System Elastance (C) which is prevented in SOX18 over-expressing mice. SOX18 over-expression attenuated the increase in BALF protein concentration in mice exposed to HTV (D). Total cell count in the bronchoalveolar lavage fluid (BALF) was elevated after HTV exposure, and this was significantly decreased by SOX18 over-expression (E). IL-1β secretion in the BALF was increased with HTV treatment, which was ameliorated by SOX18 overexpression (F). Immunoblotting analysis of HLMVECs showed that overexpression of SOX18 reduced the cyclic stretch-induced increase in pS536-NF-kB (G). *p < 0.05 versus Control, †p < 0.05 versus HTV alone. N = 4 (A); N = 3–6 (B,C); N = 6–14 (D); N = 6–12 (E); N = 43–7 (F); N = 7 (G).