1171 Single-cell RNA sequencing confirms MMP2 as the primary matrix metalloproteinase implicated in the photoaging of keratinocytes

MMP2, which encodes for a type IV collagenase targeting the basement membrane, is induced in keratinocytes by UVB an AhR-dependent and SP1-dependent fashion, likely through formation of double-stranded breaks (DSBs) DNA. While epidermal MMP2 expression correlates with signs photoaging mice, it still not yet known how relevant this model induction to human skinin situ. To assess more clinically setting, we analyzed fibroblasts single-cell RNA seq dataset sun-exposed (SE) sun-protected (SP) skin samples from donors their 20s 80s (n=8). We confirmed that among most abundantly expressed MMP genes SE relative SP skin. Analyzing subtypes keratinocytes, further found MMP2+ gradually increases superficial layers epidermis, basal granular layers, was pronounced supraspinous cells. Screening similar patterns epidermis revealed only 4 other genes—MMP15, MMP16, MMP17, MMP24—all membrane-type MMPs (MT-MMPs) activate pro-MMP2. Consistent its purported vitromodel induction, strongly correlated AHR, SP1, DNA damage sensors ATM/ATR but AP-1. Interestingly, fibroblasts, MMP15/16/17—but MMP2—robustly AHR-DSB-SP1 pathway, again AP1. In sum, these data underscore importance proteolytic activators photoaged also suggest may play distinct roles functional activation MMP2.