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Autophagy is deficient in nasal polyps: implications for the pathogenesis of the disease
Author(s) -
Chen Jeff YiFu,
Hour TzyhChyuan,
Yang SheauFang,
Chien ChenYu,
Chen HauRen,
Tsai KeLi,
Ko JenqYuh,
Wang LingFeng
Publication year - 2015
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.21456
Subject(s) - nasal polyps , autophagy , immunohistochemistry , pi3k/akt/mtor pathway , pathogenesis , medicine , western blot , protein kinase b , pathology , mucous membrane of nose , immunology , cancer research , signal transduction , microbiology and biotechnology , biology , gene , apoptosis , biochemistry
Background Nasal polyposis is characterized by persistent inflammation but the pathogenesis is complex and still debatable. Autophagy has been associated with many human health problems including chronic inflammatory airway diseases. Whether autophagy plays a role in nasal polyps and could be a therapeutic target is completely unknown. Methods We studied light chain 3 (LC3) protein expression, a common indication of autophagy, in fresh tissue specimens of 5 nasal polyps and 6 normal nasal mucosa by Western blot analysis. The results were also confirmed by immunohistochemistry (IHC) using additional 25 paraffin‐embedded nasal tissue sections. Finally the autophagic activity was validated in nasal polyp–derived fibroblasts by evaluating the number of green fluorescent protein (GFP)‐labeled LC3 puncta. Results The expression of LC3 was dramatically decreased in all 5 nasal polyp tissues. In contrast, protein kinase B–mechanistic target of rapamycin (Akt‐mTOR) signaling, an established negative regulator of autophagy, was significantly activated in these tissues. Immunohistochemical results further demonstrated a negative correlation between autophagy and nasal polyps ( p < 0.05). GFP‐LC3 puncta formation, an alternative indicator of autophagy, was also diminished in nasal polyp–derived fibroblasts ( p < 0.01). Conclusion Autophagy is deficient presumably due to suppression by high Akt‐mTOR activity in nasal polyps, which may provide a molecular basis for future mechanistic study of the disease.