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Dr. Zhuowei Hu group’s work reveals the mechanism of IL17A suppressing autophagy

Time:2013/2/28 Source:State Key Laboratory of Bioactive Substance and Function of Natural Medicines Read:2618

 

Dr. Zhuowei Hu and his group have recently published a paper entitled “Interlukin 17A inhibits autophagy through activation of PIK3CA to interrupt the GSK3B-mediated degradation of BCL2 in lung epithelial cells” in “Autophagy”, an international reputation magazine. The research paper has been published online. In a previous work by this group, researchersreported that IL-17A promotes the development and progression of pulmonary fibrosis through TGFβ1-dependent and -independent mechanisms (Mi et al, J Immunol, 2011). IL-17A stimulates not only the expression of collagen by increasing the release of the transforming growth factor beta 1 (TGFβ1) but also attenuates autophagy to suppress the collagen degradation in the fibrotic lung tissue in a TGFβ1-independent manner. Although the induction of autophagy stimulating the collagen degradation in the fibrotic lung tissue has been identified as a mechanism responsible for the antifibrotic role of targeting IL-17A, it remains to be clarified how IL-17A signaling suppresses autophagy. In this study, Dr. Hu and his group document that IL-17A-activated PI3K-GSK3β signaling cascade is involved in the regulation of the Bcl-2-Beclin-1 interaction in lung epithelial cells. In response to IL17A stimulation, PI3K p110, the catalytic subunit of PI3K, is activated to induce the phosphorylation of GSK3β at Ser9, which subsequently attenuates the interaction of GSK3β with Bcl-2. Interrupting the GSK3β and Bcl-2 interaction precludes the phosphorylation of Bcl-2 at Ser70, which triggers the ubiquitination degradation of Bcl-2. Consequently, the increased expression of Bcl-2 interferes with the activation of Beclin-1 and attenuates autophagy in these cells. The studies provide insight into the molecular mechanism and reveal a novel signal pathway for IL-17A-mediated inhibition of autophagy.
 
Autophagy”, is a unique peer-reviewed journal with an international audience that covers the following topics: macroautophagy, microautophagy, specific organelle degradation and additional autophagic processes including chaperone-mediated autophagy, the 2011 impact factor is 7.453. Under Dr. Hu direction, the first author, the 2012 session of the Ph.D. student Hong Liu, and other authors collectively completed this work. The other authors included Drs. Su Mi, Zhe Li and Fang Hua.

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