Background: Endoplasmic reticulum (ER) calcium depletion-induced ER stress is a crucial signal for keratinocyte differentiation and barrier homeostasis, but its effects on the epidermal tight junction (TJ) have not been characterized. Ultraviolet B (UVB) causes ER calcium release in keratinocytes and disrupts epidermal TJ, however, the involvement of ER stress in the UVB-induced TJ alterations remains unknown.
Objectives: To investigate the effect of ER stress by pharmacological ER calcium depletion or UVB on the TJ integrity in normal human epidermal keratinocytes (NHEK).
Methods: NHEK were exposed to ER calcium pump inhibitor thapsigargin (Tg) or UVB. ER stress markers and TJ molecules expression, TJ and F-actin structures, and TJ barrier function were analyzed.
Results: Tg or UVB exposure dose-dependently triggered unfolded protein response (UPR) in NHEK. Low dose Tg induced the IRE1α-XBP1 pathway and strengthened TJ barrier. Contrary, high dose Tg activated PERK phosphorylation and disrupted TJ by F-actin disorganization. UVB disrupted TJ and F-actin structures dose dependently. IRE1α RNase inhibition induced or exacerbated TJ and F-actin disruption in the presence of low dose Tg or UVB. High dose Tg increased RhoA activity. 4-PBA or Rho kinase (ROCK) inhibitor partially prevented the disruption of TJ and F-actin following high dose Tg or UVB.
Conclusions: ER stress has bimodal effects on the epidermal TJ depending on its intensity. The IRE1α pathway is critical for the maintenance of TJ integrity during mild ER stress. Severe ER stress-induced UPR or ROCK signalling mediates the disruption of TJ through cytoskeletal disorganization during severe ER stress.
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http://dx.doi.org/10.1016/j.jdermsci.2020.02.006 | DOI Listing |
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Graduate School, Fujian University of Traditional Chinese Medicine, Fuzhou City, People's Republic of China.
Naringenin has the potential to regulate ferroptosis and mitigate renal damage in diabetic nephropathy (DN). However, it remains unclear whether the naringenin's effects in DN are linked to its ability to regulate ferroptosis. This study investigated the potential anti-ferroptosis properties of naringenin in high glucose (HG)-induced renal tubular epithelial cell models.
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Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
There is an important concern about the potential health and environmental risks that may develop due to exposure to copper oxide nanoparticles (CuO-NPs). Selenium is an essential trace element. It supports the expression of a variety of selenoproteins.
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