Recombinant protein rVP1 upregulates BECN1-independent autophagy, MAPK1/3 phosphorylation and MMP9 activity via WIPI1/WIPI2 to promote macrophage migration.
The monocyte/macrophage is critical for regulating immune and antitumor responses. Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus induces apoptosis and inhibits migration/metastasis of cancer cells. Here, we explored the effects of rVP1 on macrophages. Our results showed that rVP1 increased LC3-related autophagosome formation via WIPI1 and WIPI2 in a BECN1-independent manner. rVP1 treatment increased macrophage migration that was attenuated by knockdown of ATG5, ATG7, WIPI1 or WIPI2 and was abolished when both WIPI1 and WIPI2 were depleted. Treatment of macrophages with rVP1 increased matrix metalloproteinase-9 (MMP9) activity and phosphorylated mitogen-activated protein kinase 1/3 (MAPK1/3), two major mediators of cell migration. Knockdown of WIPI1, WIPI2, ATG5 and ATG7 but not BECN1 attenuated the rVP1-mediated increase in MAPK1/3 phosphorylation and MMP9 activity. These results indicated that rVP1 upregulated autophagy, MAPK1/3 phosphorylation and MMP9 activity to promote macrophage migration, which was dependent on WIPI1, WIPI2, ATG5 and ATG7 but not BECN1.
Graduate Institute of Life Sciences; National Defense Medical Center; Taipei, Taiwan.
Chiao-Chun
CC
Liao
Ming-Yi
MY
Ho
Shu-Mei
SM
Liang
Chi-Ming
CM
Liang
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D036022:Capsid Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D029544:Foot-and-Mouth Disease Virus / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D036022:Capsid Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; C522812:WIPI1 protein, human; C535150:MAPK1 protein, human; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse