Effects of Hypochlorous Acid Probe CPP on Mitochondrial Function and TGF-β-Induced Fibrosis in Human Dermal Fibroblasts

There are many reported mitochondria-targeting hypochlorous acid (HCIO) probes for measuring HCIO level, but the effects of the probes on mitochondrial functions are not clear. Mitochondria have become central regulators of inflammation. ROS in mitochondria can promote inflammation by inducing calcium influx and opening of mitochondrial permeability transport pores (MPTP). Whether HCIO, one of the major components of ROS, also modulates mitochondria-related inflammatory signaling is unclear. Here, we used the mitochondria-targeting HCIO probe CPP to bind HCIO to modulate its function. First, we observed CPP targeting to mitochondria in human dermal fibroblasts (HDFs). Next, we detected the changes of mitochondrial Ca2+ concentration ([Ca2+]mito) and the opening of MPTP, and found that CPP reduced the level of [Ca2+]mito and inhibited the opening of MPTP. The results of RNA-seq further confirmed that CPP can regulate mitochondrial function. In application, we found that CPP regulated the inflammatory response of HDFs by analyzing the results of RNA-seq. Based on inflammation as a major trigger of fibrosis, we utilized rhTGFβ to induce fibrosis in HDFs and found that CPP could inhibit rhTGFβ-induced fibrosis. In conclusion, our study found that the CPP could bind HCIO to modulate the function of mitochondria, which provides enlightenment for the regulation of mitochondria by HCIO, and also provides a novel drug lead compound for the treatment of fibrosis.