RETRACTED ARTICLE: Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration

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.

Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation

“…The p38/MAPK signaling pathway is activated in multiple cells under hypoxic conditions (Hirota et al, 2015; Park and Rongo, 2016; Chen et al, 2018), and MKK6 is recognized as a specific upstream regulator of p38/MAPK signaling (Stramucci et al, 2018). As shown in our previous studies, p38/MAPK was upregulated through ROS generation in keratinocytes under hypoxia stress (Zhang et al, 2019). Meanwhile, the activation of the p38/MAPK pathway is implicated in MAP4 phosphorylation in hypoxic cardiomyocytes (Hu et al, 2014; Li et al, 2018).…”

A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299

“…As Western blotting is considered only a semi-quantitative approach, we utilized the microarray assay to perform a complex screening of the effects of Lys05 on the level of mRNA (data are available in Supplementary Tables S1 and S2, and GEO repository: GSE138650), which led us to further examination of two particular genes using qRT-PCR: SQSTM1 and Bcl2 interacting protein 3 ( BNIP3 ). These genes are well-known to be associated with autophagy [15,16]. Administration of Lys05 and/or irradiation (2 Gy) led to a significant increase in SQSTM1 expression and decrease in BNIP3 expression in the groups of cells treated either by Lys05 alone or by its combination with IR both after 24 and 48 h (Figure 3B).…”

Sulforaphane-cysteine inhibited migration and invasion via enhancing mitophagosome fusion to lysosome in human glioblastoma cells

“…Cell motility involves drastic structural changes, a process that demands high levels of energy and fully functional mitochondria whose quality and quantity are balanced by mitophagy 42 . Bnip3 is a proapoptotic atypical BH3-only protein that has been reported to induce apoptosis, necrosis, or autophagy relying on the type of stress and cellular context 43 . As a hallmark of mitophagy, upregulation of Bnip3 was associated with an increase of autophagy flux and mitochondrial protein degradation, as well as mitophagosome formation; loss of Bnip3 led to the accumulation of damaged mitochondria 44 .…”