Early-age-related changes in VCP expression correlates with ubiquitin accumulation and hyper-inflammatory response.

<p>The longitudinal lungs sections from control, CLP or i.t. <i>Pa</i>-LPS (1 µg/gm bw) induced murine model (n = 3–4) were processed for histological evaluation. (<b>A</b>) We verified by TUNEL assay that accumulation of damaged- or misfolded- proteins leads to an increase in lung cell apoptosis in the adult mice by quantifying the changes in number of TUNEL positive cells. This is further exacerbated by <i>Pa</i>-LPS- or CLP- induced injury, verifying the correlation of ubiquitinated protein accumulation to increased apoptosis. The bottom panel of each staining shows the spearman's correlation coefficient analysis of the number of apoptotic cells in pediatric- and adult- mice (10 uniform representative areas from each mouse). (<b>B</b>) The adult mice show a constitutive increase in inflammation as compared to the pediatric group (H&E) that correlates with an increase in NFκB (C) and VCP (D) protein levels. The right panel of each staining shows the spearman's correlation coefficient analysis of fluorescence intensity in pediatric- and adult- mice (10 uniform representative areas from each mouse). (<b>E</b>) The <i>Pa</i>-LPS and CLP treatments induce the accumulation of ubiquitinated proteins that correlates with further increase in protein levels of NFκB (C) and VCP (D). <i>Data confirms that early-age-related proteostasis-imbalance augments Pa-LPS or sepsis induced injury</i>.