SOD3 Suppresses the Expression of MMP-1 and Increases the Integrity of Extracellular Matrix in Fibroblasts

Abstract

The superoxide dismutase (SOD) family functions as a reactive oxygen species (ROS)-scavenging system by converting superoxide anions into hydrogen peroxide in the cytosol (SOD1), mitochondria (SOD2), and extracellular matrix (SOD3). In this study, we examined the potential roles of SOD family members in skin aging. We found that SOD3 expression levels were significantly more reduced in the skin tissues of old mice and humans than in young counterparts, but SOD1 and SOD2 expression levels remained unchanged with aging. Accordingly, we analyzed the effects of SOD3 on intracellular ROS levels and the integrity of the extracellular matrix in fibroblasts. The treatment of foreskin fibroblasts with recombinant SOD3 reduced the intracellular ROS levels and secretion of MMP-1 while increasing the secretion of type I collagen. The effects of SOD3 were greater in fibroblasts treated with the TNF-α. SOD3 treatment also decreased the mRNA levels and promoter activity of MMP-1 while increasing the mRNA levels and promoter activities of COL1A1 and COL1A2. SOD3 treatment reduced the phosphorylation of NF-κB, p38 MAPK, ERK, and JNK, which are essential for MMP-1 transactivation. In a three-dimensional culture of fibroblasts, SOD3 decreased the amount of type I collagen fragments produced by MMP-1 and increased the amount of nascent type I procollagen. These results demonstrate that SOD3 reduces intracellular ROS levels, suppresses MMP-1 expression, and induces type I collagen expression in fibroblasts. Therefore, SOD3 may play a role in delaying or preventing skin aging.

Multiomics Approach Reveals Serum Biomarker Candidates for Congenital Zika Syndrome

“…Also, it was observed that cells treated with SOD3 reduced their intracellular ROS level and secretion of MMP-1 proteins, while the cells increased the secretion of COL1. 51 The identification of SOD3 only in non-CZS patients suggests a unique antioxidant mechanism and also could be related to the different collagen expression levels between non-CZS and CZS fetuses described in other studies. 50,54 Remarkably, there is an exacerbated disruption of the host immune system caused by ZIKV, and this disruption is observed even after the acute phase of infection.…”

Increased anti‐oxidative action compensates for collagen tissue degeneration in vitiligo dermis

“…QRT‐PCR of anti‐oxidative enzymes, including CAT , PARK7 , and six target genes of the NRF2 pathway, showed that the expression of SOD3 and GPX3 was significantly upregulated in vitiligo fibroblasts. It is known that SOD3 suppresses the expression of MMP1 and increases the integrity of the extracellular matrix in fibroblasts (Kim et al, 2022). We hypothesized that the NRF2 pathway signaling was enhanced in vitiligo fibroblasts.…”

Anti-PTK7 Monoclonal Antibodies Inhibit Angiogenesis by Suppressing PTK7 Function

“…Next, the cells were stimulated with 10 ng/mL human VEGF for 2 min to analyze receptor phosphorylation, 1 h to analyze the phosphorylation of FAK [ 31 , 32 ], or 10 min to analyze the phosphorylation of other signaling molecules. The cells were then lysed with radioimmunoprecipitation assay lysis buffer [ 33 ] containing 1 mM Na 3 VO 4 and 5 mM NaF. Cell lysates were resuspended in SDS sample buffer and subjected to Western blotting.…”