| Abstract: | Wound healing may be disrupted by lipopolysaccharide (LPS)-induced mitochondrial dysfunction, inflammation, and excessive oxidative stress, which can lead to undesirable consequences. The haematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) is a mitochondrial matrix protein that regulates mitochondrial function. This study aimed to comprehensively identify the role of HAX-1 in the inhibition of LPS-induced mitochondrial dysfunction and apoptosis in human dermal fibroblasts (HDFs). HAX-1 expression was assessed in the HDF-a cell line using real-time polymerase chain reaction, western blotting, and immunohistochemical staining. The viability, migration, and apoptosis of HDF-a cells were evaluated using the water-soluble tetrazolium-1 assay, transwell assay, and flow cytometry analysis, respectively. Mitochondrial function was evaluated based on reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm). Our results demonstrated that LPS stimulation markedly repressed HAX-1 expression in HDFs and silencing of HAX-1 led to mitochondrial ROS accumulation, ΔΨm disruption, and abnormal mitochondrial morphology. Accordingly, overexpression of HAX-1 or administration of metformin enhanced mitochondrial fusion and normalized mitochondrial dynamics, thereby reversing LPS-induced mitochondrial dysfunction, fibroblast apoptosis, and viability and migration inhibition in HDF-a cells. These data support a mechanism wherein HAX-1 plays a crucial role in LPS-induced fibroblast apoptosis in a mitochondria-dependent manner. |
