Expression of miR15b5p, miR215p, and SMAD7 in Lung Tissue of Sulfur Mustardexposed Individuals with Longterm Pulmonary Complications

Sulfur mustard (SM)exposed individuals develop late pulmonary complications, which are associated with chronic inflammation and fibrotic changes in the lung tissue. MicroRNAs are known to act as important regulators of inflammatory responses, including inflammation and fibrosisrelated cytokine signaling. In this study, we investigated the expression miR15b5p and miR215p, two regulators of TGF #x3B2; signaling, as well as their target molecule, SMAD7, in lung tissues from SMexposed and control individuals. Total RNA was extracted from formalinfixed paraffinembedded (FFPE) lung tissue biopsies obtained during surgery from SMexposed (n=20) or control (n=20) cases. Quality of the extracted RNA was evaluated by an Agilent Bioanalyzer and RNA was quantified using a NanoDrop. MiR215p, miR15b5p and SMAD7 expression levels were measured by realtime RTPCR. miR215p expression levels were significantly decreased (2.7 fold) in the lung tissues from SMexposed individuals compared with tissues obtained from the control group (p=0.02). There were no significant differences in miR15b5p expression levels between the two groups (p=0.94). Interestingly, SMAD7 expression levels were significantly higher (5.8 fold) in SMexposed individuals #x2019; lung tissues compared with the control group (p=0.045). Our data indicate that exposure to sulfur mustard affects the expression of miR215p as well as its target, SMAD7, in lung tissues many years after exposure. Considering the role of SMAD7 in the regulation of TGF #x3B2; signaling, these changes might point to a potential mechanism by which SMexposure regulates inflammatory/fibrotic alterations in lung tissue.