MultiOMICs of WTC-Particulate Induced Persistent Airway Hyperreactivity: Role of Receptor for Advanced Glycation End Products.

MultiOMICs of WTC-Particulate Induced Persistent Airway Hyperreactivity: Role of Receptor for Advanced Glycation End Products. Am J Respir Cell Mol Biol. 2020 Apr 21;: Authors: Haider SH, Veerappan A, Crowley G, Ostrofsky D, Mikhail M, Lam R, Wang Y, Sunseri M, Kwon S, Prezant DJ, Liu M, Schmidt AM, Nolan A Abstract Pulmonary disease after World Trade Center particulate matter(WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We utilized a murine model and a multiOMIC assessment to understand the role of RAGE in the pulmonary long-term effects of a single high intensity exposure to WTC-PM. After 1-month(1-M), WTC-PM exposed wild-type(WT) mice had airway hyperreactivity(AHR) while RAGE-deficient(Ager-/-) were protected. PM-exposed WT mice also had histologic evidence of airspace disease while Ager-/- remained unchanged. Inflammatory mediators such as G-CSF, IP-10, and KC were differentially expressed after WTC-PM exposure. WTC-PM induced α-SMA, DIAPH1, RAGE and significant lung collagen deposition in WT compared to Ager-/-. Compared to WT with PM exposure, relative expression of phosphorylated to total CREB and JNK were significantly increased in the lung of PM-exposed Ager-/-, whereas Akt was decreased. Random forests of the refined lung metabolomic profile classified subjects with 92% accuracy; principal components analysis ...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research