Abstract
Background: It has been reported that the rHuKGF supplementation has the possibility to induce alveolar epithelium proliferation in emphysematous lungs. Also, it’s evident that keratinocyte growth factor stimulate VEGF synthesis which in turn confers the maintenance of the normal lung structure via Akt pathway. Objective: To study the effect of rHuKGF in the emphysematous mice lungs on AKT mediated signalling pathway. Methods: Three experimental groups [i.e., emphysema (ES), therapy for emphysema (EK) and control (SS)] were prepared. Subsequently, lungs from each mouse were collected for histopathology & QPCR based analyses and protease levels were studied by gelatin zymography. Results: Histopathological based analysis clearly represented that the loss of alveolar septa was reversed in (EK), which were significantly lost in (ES). The mRNA levels of VEGF, VEGFR 2, PI3K & AKT were significantly downregulated in (ES) than (SS) & were highly upregulated in (EK) when compared with (ES). Moreover, the mRNA levels of these genes were well comparable with (SS). The mRNA levels of Pten, Caspase-9 & Bad were significantly upregulated in (ES) than (SS) & were highly downregulated in (EK) when compared with (ES). Independently, using BAL fluid, enzymatic activity was detectable for MMP-2 by zymography. Densitometry based quantitative analysis of gels revealed that MMP-2 activity was induced to 2 fold in (ES) than (SS) and (EK) shows 3.5 fold reduction than (ES). Conclusion: The therapeutic application of exogenous rHuKGF into emphysematous lungs is able to induce alveolar cell survival pathway in the emphysematous lung.
- © 2013 ERS
