Research Paper Volume 13, Issue 5 pp 6406—6419
Ablation of CRBN induces loss of type I collagen and SCH in mouse skin by fibroblast senescence via the p38 MAPK pathway
- 1 School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
- 2 Integrated Institute of Bio-Medical Research, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
- 3 Department of Physiology, BK21 Plus Project Team, College of Medicine, Smart Marine Therapeutics Center, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
- 4 Department of Life Science and Environmental Biochemistry, and Life and Industry Convergence Research Institute, Pusan National University, Miryang, Republic of Korea
- 5 Department of Dermatology, Inje University Busan Paik Hospital, College of Medicine, Smart Marine Therapeutics Center, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
Received: November 13, 2020 Accepted: February 9, 2021 Published: March 3, 2021https://doi.org/10.18632/aging.202744
How to Cite
Copyright: © 2021 Jeon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cereblon (CRBN) is a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) complex that mediates the ubiquitination of several substrates. In this study, CRBN knockout (KO) mice exhibited decreased levels of stratum corneum hydration (SCH) and collagen I expression with an elevated protein level of matrix metalloprotease 1 (MMP1). The absence of cereblon in the skin of CRBN KO mice mimics the damage caused by narrowband ultraviolet B (NB-UVB). The primary CRBN deficient mouse embryonic fibroblasts (MEFs) undergo G2/M-arrested premature senescence via protein signaling of p38 MAPK and its dependent p53/p21pathway. The absence of CRBN induced the markers of cellular senescence, such as the senescence-associated heterochromatin foci (SAHF), SA-β-Gal staining, and p21 upregulation while the ectopic expression of CRBN reversed the phenotypes of SA-β-Gal staining and p21 upregulation. Reversion of the decreased protein level of collagen I was demonstrated after the reintroduction of the CRBN gene back into CRBN KO MEFs, validating the promising role of CRBN as a potential regulator for the function of the skin barrier and its cellular homeostasis.
CRBN KO: cereblon knock-out; SCH: stratum corneum hydration; MEFs: mouse embryonic fibroblasts.