Is the Mitochondrial Function of Keloid Fibroblasts Affected by Cytoglobin?

Abstract

Background: A keloid is a benign skin tumour characterised by excessive proliferation of fibroblasts, a process that requires a sufficient amount of energy. The energy needs are associated with adequate oxygen (O2) flow and well-functioning mitochondria. It is known that cytoglobin (CYGB) has a function in O2 distribution. The aim of the present study was to explore whether the inhibition of CYGB expression caused impaired mitochondrial function of keloid fibroblasts. Methods: An in vitro study was conducted on a keloid fibroblast derived from our previous study. The study was carried out in the laboratory of the Biochemistry & Molecular Biology Department, Faculty of Medicine, Universitas Indonesia (FMUI), from July to December 2018. CYGB expression was inhibited by small interfering ribonucleic acid (siRNA) and CYGB. Analysis of mitochondrial function was observed through peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a mitochondrial biogenesis marker and the activity of the succinate dehydrogenase (SDH) enzyme in mitochondria. Results: The CYGB gene and protein were downregulated after treatment with CYGB siRNA. Inhibition of CYGB expression with siRNA also tended to decrease the levels of PGC-1α messenger ribonucleic acid (mRNA) and protein, as well as SDH enzyme activity. Conclusion: Inhibition of CYGB expression with siRNA tended to decrease mitochondrial biogenesis and function. This may be useful for understanding the excessive proliferation of fibroblasts in keloids and for development of treatment for keloids.

Inhibition of ALA dehydratase activity in heme biosynthesis reduces cytoglobin expression which is related to the proliferation and viability of keloid fibroblasts

“…( 16 ) Furthermore, it showed that inhibition of CYGB mRNA expression using siRNA tends to reduce the expressions of PGC1-α mRNA and protein, which are markers of mitochondrial biogenesis, and the activity of the SDH enzyme, which plays a role in the process of energy formation in the TCA cycle. ( 15 ) Inhibition of CYGB expression using siRNA tends to decrease mitochondrial function and biogenesis, which can interfere with the production of the energy needed to support the viability and proliferation of keloid fibroblasts. Our present study supports our previous studies regarding the effect of CYGB on the viability and proliferation of keloid fibroblasts.…”

“…( 14 ) Our previous study showed that inhibiting CYGB expression using siRNA reduces mitochondrial biogenesis in keloid fibroblasts, as shown by the lower expression levels of PGC1-mRNA and protein. ( 15 ) In addition, the inhibition of CYGB expression using siRNA tends to reduce the activity level of the enzyme succinate dehydrogenase (SDH), which plays a role in the energy formation process in the tricarboxylic acid (TCA) cycle. ( 15 ) Although inhibition of CYGB expression using siRNA tends to decrease mitochondrial biogenesis and SDH activity levels, its effect on keloid fibroblast proliferation is still unclear.…”

“…( 15 ) In addition, the inhibition of CYGB expression using siRNA tends to reduce the activity level of the enzyme succinate dehydrogenase (SDH), which plays a role in the energy formation process in the tricarboxylic acid (TCA) cycle. ( 15 ) Although inhibition of CYGB expression using siRNA tends to decrease mitochondrial biogenesis and SDH activity levels, its effect on keloid fibroblast proliferation is still unclear. ( 16 ) Hence, the aim of this study was to analyze the effect of heme synthesis inhibition on CYGB expression levels and its correlation with the proliferation and viability of fibroblast keloids.…”

Study of the Inhibitory Effects of Vitamin E Derivatives on Mitochondrial Complex Ii Subunit Using Molecular Docking

“…SDH comprises SDHA, SDHB, SDHC, SDHD, SDHAF1, SDHAF2 subunits [3], and exhibits tumor-suppressing effects [4]. A decreased SDH activity leads to the accumulation of succinate, thus triggering the stabilization of the hypoxia-inducible factor (HIF) through competitive inhibition of HIF prolyl hydroxylases [5]. A stabilized HIF triggers pseudo-hypoxia signaling, leading to angiogenesis, dysregulation of cell proliferation, and adhesion [6].…”