Ultraviolet B Irradiation Alters the Level and miR Contents of Exosomes Released by Keratinocytes in Diabetic Condition

Abstract

Ultraviolet B (UVB) stimulates the generation of extracellular vesicles, which elicit systemic effects. Here, we studied whether UVB affects the release and microRNA (miR) content of keratinocyte exosomes (EXs) in diabetic conditions. In vitro, we examined the UVB effects on affecting EX release from keratinocyte HaCaT cells (HaCaT-EX) pretreated with high glucose. HaCaT-EX functions were evaluated on Schwann cells (SCs). In vivo, UVB-induced miR change in skin EXs of diabetic db/db mice was analyzed. The miRs of interest were validated in HaCaT-EXs. We found that: (1) UVB promoted HaCaT-EX generation in dose-and timedependent manners; 100 and 1800 J m −2 of UVB had the most prominent effect and were selected as effective low-and high-fluence UVB in vitro. (2) A total of 13 miRs were differentially expressed >3-fold in skin EXs in UVB-treated db/db mice; miR-126 was the most up-regulated by low-fluence UVB. (3) Functional studies revealed that the SC viability was improved by low-fluence UVB HaCaT-EXs, while worsened by high-fluence UVB HaCaT-EXs. (4) MiR-126 inhibitor attenuated the effects induced by low-fluence UVB HaCaT-EXs. Our data have demonstrated that low-and high-fluence UVBs promote HaCaT-EX generation but differentially affect exosomal miR levels and functions under diabetic conditions.

Extracellular Vesicles: A New Star for Gene Drug Delivery

“…Compared with other physical methods, it is a prospective method for EVs loading and generation in a single step. In addition, radiation, including X-ray, 97 gamma ray, 98 and ultraviolet, 99 has been shown to increase the secretion of EVs in various cells. However, the application of radiation can cause cell damage and affect the experimental results, such as the production of reactive oxygen species under ultraviolet irradiation which can induce oxidative cell damage if its level exceeds the antioxidant defense mechanism of the body.…”

Exercise-Intervened Endothelial Progenitor Cell Exosomes Protect N2a Cells by Improving Mitochondrial Function

“…Both R-EPC-EX and R-EPC-EX ET expressed the exosomal markers (CD63, Tsg 101) and EPC-specific marker (CD34, VEGFR2) as reported (Chen et al, 2022) [22]. Before the co-culture experiment for the in vitro track, all EPC-EXs were labeled with a red fluorescent dye PKH26.…”

“…The levels of miR-27a in R-EPC-EXs, R-EPC-EX ET , and N2a after co-incubation was determined by qRT-PCR, as we have reported [50]. In brief, the total miRs were extracted using the Trizol reagent, and the RNA concentration was measured using NanoDrop 2000 (Thermo Fisher Scientific).…”

Cutaneous changes in diabetic patients: Primed for aberrant healing?

“… 47,48 ROS such as nitric oxide has potent regulatory effects on keratinocyte proliferation and differentiation, but the point at which ROS or other signalling molecules transition from functional and necessary to destructively dysfunctional has not yet been elucidated 49,50 . Hyperglycaemic conditions in keratinocytes also increase sensitivity to ultraviolet exposure, with an increased release of exosomes and their miRNA content that may influence inter‐cellular communication 51 …”