Assessing mitochondrial function, oxidative stress, and vitamin D status in dark-skinned patients with keloid disease

Abstract

Keloid disease is a challenging condition that occurs worldwide and is mainly experienced by dark-skinned population groups. Keloids are characterised by excessive fibrous tissue formation. Unlike normal scars, keloids extend beyond the boundaries of the original wound and continue to grow for months or years. They are firm, shiny, and irregular in shape. Symptoms, such as itching and pain, are associated with keloid disease. Keloids tend to appear in areas such as the chest, shoulders, earlobes, and upper back and have a high recurrence rate after treatment. Recent evidence has demonstrated that mitochondria play a critical role in meeting the substantial energy requirements of wound repair and facilitate healthy wound healing through cytoskeletal remodelling, mediated by mitochondrial morphological alterations and reactive oxygen species (ROS) signalling pathways. Although the exact pathophysiology remains unclear, emerging evidence suggests that mitochondrial dysfunction and oxidative stress play critical roles. Vitamin D (Vit D), known for its antioxidant properties and its influence on mitochondrial health, may also be implicated, especially in populations prone to Vit D deficiency.

This study aimed to assess mitochondrial function, oxidative stress, and Vit D status in dark-skinned patients with keloid disease. Specifically, we explored the complex correlation between mitochondrial dysfunction and oxidative stress, as indicated by malondialdehyde (MDA) levels over a range of Vit D concentration levels.

Keloid tissue and blood samples were collected from a cohort of patients with dark-skinned keloids. A total of 44 patients were included in the study, of which 27 were male and 17 were female and were between the ages of 18 ‒ 40 years old. Vitamin D status was assessed by measuring plasma Vit D concentrations, and lipid peroxidation was assessed by measuring MDA levels in the blood plasma, which is a biomarker for oxidative stress in cells. Mitochondrial morphology was examined using Transmission Electron Microscopy (TEM), focusing on the mitochondrial size, membrane integrity, and abundance. Correlation analysis was conducted to evaluate the complex relationship between mitochondrial integrity, MDA levels, and Vit D status.

The results revealed a significant negative correlation (r = -0.52) between viable mitochondrial DNA (mtDNA) and MDA levels, indicating that higher levels of oxidative stress are associated with greater mitochondrial dysfunction. Patients that had lower concentration levels of Vit D showed elevated MDA levels within their blood plasma and more severe mitochondrial damage, such as no clear double membrane, improper folding of the cisternae, and small mitochondria compared to those with higher concentration levels of Vit D. In contrast, 32 dark-skinned patients had adequate Vit D levels. The TEM analysis highlighted significant mitochondrial abnormalities in keloid cells, including reduced size, damaged membranes, and decreased mitochondrial quantity. These defects were more pronounced in patients with Vit D deficiency.

In conclusion, the findings of this study suggest that mitochondrial integrity and oxidative stress are key components of keloid pathogenesis, particularly in dark-skinned patients with low concentration levels of Vit D. The significant association between reduced mitochondrial function and increased oxidative stress highlights the potential role of Vit D in modulating these processes. This study emphasises the need for further research on Vit D supplementation along with calcium as a therapeutic intervention for keloid disease, particularly in dark-skinned individuals prone to low concentration levels of Vit D and keloid formation.