Coordinated activation of a cluster of MMP genes in response to UVB radiation

Abstract

Ultraviolet (UV) B radiation is a dangerous environmental stressor, which can lead to photoaging, inflammation, immune suppression and tumour formation. A recent report has shown the transcriptional activation of several skin-specific genes including matrix metalloproteases (MMPs) in response to UV irradiation. Here, we use a novel human keratinocyte model, HKerE6SFM, to demonstrate that UVB activates the transcription of most members of the 11q22.3 MMP gene cluster including MMP13, MMP12, MMP3, MMP1 and MMP10. Curiously, the expression of the well-characterized UVB-inducible MMP9, which is located outside of the cluster, remains unchanged. In accordance with the increased expression of the MMP gene cluster upon UVB irradiation, RNA polymerase II showed increased occupancy at their promoters following UVB irradiation. The results also demonstrate increased acetylated histone H3K9 levels at the promoters of the MMP13, MMP12, MMP3, MMP1 and MMP10 genes. These findings suggest a coordinated transcriptional activation of genes in the MMP cluster at 11q22.3 and that acetylation of histone H3 at lysine 9 has an important role in the UVB-dependent enhancement of transcription of MMP genes in this region.

SerpinB2 is involved in cellular response upon UV irradiation

“…Ultraviolet light induced DNA damage response is an extensively studied process, since improper or delayed repair of the errors could lead to cancerous malformations. In our recent study we have identified UV-induced genes in an immortalized keratinocyte cell line, Hker E6SFM, by performing a microarray experiment 23 . By comparing the mRNA profiles of non-treated and UV treated cells, 244 genes showed significantly altered expression.…”

Protective Effect of Baicalin Against TLR4‐mediated UVA‐induced Skin Inflammation

“…Our results in fact showed downregulation of p47 phox , a key subunit of NADPH oxidase, after baicalin treatment. Furthermore, UVA activation of MMPs and subsequent degradation of collagen is a major mechanism of photoaging . Our study showed that baicalin was associated with reduced levels of two particular enzymes, MMP1 and MMP9; however, the mechanism behind these decreases remains unclear.…”

The Key Role of DNA Methylation and Histone Acetylation in Epigenetics of Atherosclerosis

“… 73 MMP cluster genes are coordinately increased in proportion to H3K9 acetylation. 74 In addition, sodium butyrate, an HDAC inhibitor, increases the secretion of pro-MMP9 and pro-MMP2 via H4 hyperacetylation. 75 The increased expression and activity of MMPs are obviously found in atherosclerosis plaques and promote plaque rupture.…”