Differential effects of the Src family tyrosine kinases Yes and Fyn on lipopolysaccharide-induced lung injury in mice
Year: 2021
Type: article
Abstract: Endothelial cell apoptosis is an early event in the development of acute lung injury (ALI). We have previously found that the Src family tyrosine kinase (STK) Yes activates caspase-3, whereas the STK Fyn inhibits caspase-3 activation in cultured pulmonary endothelial cells. We hypothesized that deficiency in Yes or Fyn in mice would have differential effects on lipopolysaccharide (LPS)-induced ALI. Mice were treated with LPS (10 mg/kg ip) for 24 h. Histological evidence of lung injury was greater in LPS-treated wild-type mice than in vehicle-treated wild-type mice, and the LPS-induced histological evidence of lung injury was attenuated in yes−/− mice and enhanced in fyn−/− mice. In wild-type or fyn−/− mice, LPS resulted in greater lung wet-to-dry weight ratios than in controls, whereas in yes−/− mice lung, wet-to-dry weight was similar between LPS and controls. LPS-exposed fyn−/− mice had greater respiratory system resistance and lower respiratory system compliance than did LPS-exposed wild-type mice. TUNEL positive cells in the lung following LPS treatment were greater in the fyn−/− mice and lower in the yes−/− mice compared with that in the wild-type mice. Following LPS treatment lung protein levels of PECAM-1 were lower in fyn−/− mice than in controls or yes−/− mice. LPS treatment increased cleaved caspase-3 protein levels in wild-type mice, whereas LPS-induced caspase-3 activation was attenuated in yes−/− mice and enhanced in fyn−/− mice. These results indicate that LPS-induced ALI is positively mediated via Yes-related mechanisms and negatively mediated by Fyn-related mechanisms.
Authors: Jennifer K. Trittmann, Yi Jin, Yusen Liu, Leif D. Nelin
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3171259798