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Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration.
- Source :
-
Cell death & disease [Cell Death Dis] 2019 Mar 08; Vol. 10 (3), pp. 234. Date of Electronic Publication: 2019 Mar 08. - Publication Year :
- 2019
-
Abstract
- BNIP3 is an atypical BH3-only member of the Bcl-2 family with pro-death, pro-autophagic, and cytoprotective functions, depending on the type of stress and cellular context. Recently, we demonstrated that BNIP3 stimulates the migration of epidermal keratinocytes under hypoxia. In the present study found that autophagy and BNIP3 expression were concomitantly elevated in the migrating epidermis during wound healing in a hypoxia-dependent manner. Inhibition of autophagy through lysosome-specific chemicals (CQ and BafA1) or Atg5-targeted small-interfering RNAs greatly attenuated the hypoxia-induced cell migration, and knockdown of BNIP3 in keratinocytes significantly suppressed hypoxia-induced autophagy activation and cell migration, suggesting a positive role of BNIP3-induced autophagy in keratinocyte migration. Furthermore, these results indicated that the accumulation of reactive oxygen species (ROS) by hypoxia triggered the activation of p38 and JNK mitogen-activated protein kinase (MAPK) in human immortalized keratinocyte HaCaT cells. In turn, activated p38 and JNK MAPK mediated the activation of BNIP3-induced autophagy and the enhancement of keratinocyte migration. These data revealed a previously unknown mechanism that BNIP3-induced autophagy occurs through hypoxia-induced ROS-mediated p38 and JNK MAPK activation and supports the migration of epidermal keratinocytes during wound healing.
- Subjects :
- Animals
Autophagy-Related Protein 5 antagonists & inhibitors
Autophagy-Related Protein 5 genetics
Autophagy-Related Protein 5 metabolism
Cell Hypoxia
Cell Line
Cell Movement physiology
Cell Proliferation physiology
Humans
Keratinocytes ultrastructure
MAP Kinase Kinase 4 genetics
MAP Kinase Kinase 4 metabolism
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Mitochondrial Proteins genetics
Proto-Oncogene Proteins genetics
Reactive Oxygen Species metabolism
Signal Transduction genetics
Signal Transduction physiology
Wound Healing genetics
Wound Healing physiology
p38 Mitogen-Activated Protein Kinases genetics
p38 Mitogen-Activated Protein Kinases metabolism
Autophagy physiology
Keratinocytes metabolism
Membrane Proteins metabolism
Mitochondrial Proteins metabolism
Proto-Oncogene Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 30850584
- Full Text :
- https://doi.org/10.1038/s41419-019-1473-9