ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via mTORC1-TFEB-BLOC1S3 axis.
J Nanobiotechnology
; 22(1): 312, 2024 Jun 05.
Article
in En
| MEDLINE
| ID: mdl-38840221
ABSTRACT
Zinc oxide nanoparticles (ZNPs) are widely used in sunscreens and nanomedicines, and it was recently confirmed that ZNPs can penetrate stratum corneum into deep epidermis. Therefore, it is necessary to determine the impact of ZNPs on epidermis. In this study, ZNPs were applied to mouse skin at a relatively low concentration for one week. As a result, desmosomes in epidermal tissues were depolymerized, epidermal mechanical strain resistance was reduced, and the levels of desmosomal cadherins were decreased in cell membrane lysates and increased in cytoplasmic lysates. This finding suggested that ZNPs promote desmosomal cadherin endocytosis, which causes desmosome depolymerization. In further studies, ZNPs were proved to decrease mammalian target of rapamycin complex 1 (mTORC1) activity, activate transcription factor EB (TFEB), upregulate biogenesis of lysosome-related organelle complex 1 subunit 3 (BLOC1S3) and consequently promote desmosomal cadherin endocytosis. In addition, the key role of mTORC1 in ZNP-induced decrease in mechanical strain resistance was determined both in vitro and in vivo. It can be concluded that ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via the mTORC1-TFEB-BLOC1S3 axis. This study helps elucidate the biological effects of ZNPs and suggests that ZNPs increase the risk of epidermal fragmentation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zinc Oxide
/
Cadherins
/
Endocytosis
/
Epidermis
/
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/
Mechanistic Target of Rapamycin Complex 1
Limits:
Animals
Language:
En
Journal:
J Nanobiotechnology
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido