TAZ Reduces UVA-mediated Photoaging through Regulates Cell Proliferation in Skin Fibroblasts.

The transcriptional co-activator with PDZ-binding motif (TAZ) is a significant transcription factor downstream of the Hippo pathway regulating organ size, tissue regeneration, cell proliferation and apoptosis. Here, we report on TAZ in response to photoaging mediated by repeated UVA irradiation in skin fibroblasts. Continuous UVA irradiation caused a decrease in TAZ and targeted CTGF mRNA and protein expression in fibroblasts, accompanied by reduced cell proliferation, DNA damage, and cell cycle arrest in G1 phase and S phase reduction. Furthermore, P16 and P21 expression levels were increased, whereas Lamin B1 and Lamin A/C expression were decreased as a result of repeated UVA exposure. We further demonstrated that TAZ reduction enables photoaging caused by continuously UVA-irradiated fibroblasts. TAZ overexpression decreases G1 phase, augments the S phase and reduces P16 and P21 protein expression levels in fibroblasts. However, TAZ overexpressing cells exposed to chronic-UVA radiation show induced G1 phase arrest, an S phase reduction, and elevated P16 and P21 protein levels in fibroblasts, compared with TAZ overexpression cells. These findings suggest a novel function of TAZ to reduce photoaging in fibroblasts. This regulation implies that TAZ might be a viable therapeutic target for photoaging or UVA-related skin disorders.

ALA_PDT Promotes Ferroptosis-Like Death of Mycobacterium abscessus and Antibiotic Sterilization via Oxidative Stress.

Mycobacterium abscessus is one of the common clinical non-tuberculous mycobacteria (NTM) that can cause severe skin infection. 5-Aminolevulinic acid photodynamic therapy (ALA_PDT) is an emerging effective antimicrobial treatment. To explore whether ALA_PDT can be used to treat M. abscessus infections, we conducted a series of experiments in vitro. We found that ALA_PDT can kill M. abscesses. Mechanistically, we found that ALA_PDT promoted ferroptosis-like death of M. abscesses, and the ROS scavenger N-Acetyl-L-cysteine (NAC) and ferroptosis inhibitor Ferrostatin-1 (Fer-1) can mitigate the ALA_PDT-mediated sterilization. Furthermore, ALA_PDT significantly up-regulated the transcription of heme oxygenase MAB_4773, increased the intracellular Fe2+ concentration and altered the transcription of M. abscessus iron metabolism genes. ALA_PDT disrupted the integrity of the cell membrane and enhanced the permeability of the cell membrane, as evidenced by the boosted sterilization effect of antibiotics. In summary, ALA_PDT can kill M. abscesses via promoting the ferroptosis-like death and antibiotic sterilization through oxidative stress by changing iron metabolism. The study provided new mechanistic insights into the clinical efficacy of ALA_PDT against M. abscessus.