PGRN deficiency inhibits autophagy and apoptosis of skin tissues in mice with IMQ-induced dermatitis

Abstract:

Objective：To investigate the differences in inflammation and autophagy in imiquimod（IMQ）-induced dermatitis model be－tween progranulin-deficient（PGRN-/-） mice and wild-type（WT） mice. Methods：The psoriasis-like dermatitis model was established by smearing the back skin of mice（44 WT mice and 16 PGRN-/- mice） with IMQ. Western blot，quantitative polymerase chain reac－tion(qPCR），hematoxylin and eosin（HE） staining were used to detect the changes in the tissue structure， inflammatory factors[（inter－leukin-6，IL-6），（interleukin-10，IL-10），（tumor necrosis factor-α，TNF-α），（nitric oxide synthase 2，NOS2），（cyclo-oxygen-ase 2，COX2），（interleukin-1β，IL-1β）]，apoptosis-related protein（cysteinyl aspartate specific proteinase 3，Caspase3） and autophagy-related proteins[（microtubule-associated protein 1 light chain 3，LC3），（ubiquitin binding protein，P62），（autophagy related protein 5，ATG5），（autophagy related protein 7，ATG7），（complex of autophagy related protein 5 and 12，ATG5-ATG12）] of the mice. Results：The mouse model of psoriasis-like dermatitis was successfully established. Significant thickening of epithelial tissues，increased infil－tration of inflammatory cells，and more angiogenesis were observed in the WT mouse model，with the highest expression levels of IL-6，IL-10，TNF-α，NOS2，and COX2 observed on the sixth day（P<0.05），and autophagy increased with time. In addition，the proportion of spleen increased significantly on the sixth day（P<0.05），and the expression levels of inflammatory factors IL-6，IL-10，TNF-α，NOS2，COX2，and IL-1β were highest（P<0.05）. Compared with the WT mouse model，the PGRN-/- mouse model showed more significant thickening of the back skin，higher expression levels of inflammatory factors IL-6 and NOS2（P<0.05），and signifi－cantly reduced levels of autophagy and apoptosis（P<0.05）. Conclusion：The dermatitis model is successfully established both in the WT mice and the PGRN-/- mice on the sixth day. The symptoms are more severe in the PGRN-/- mouse model than in the WT mouse model，which may be related to PGRN deficiency due to its role in impeding autophagy.