Does vitamin D deficiency predispose to keloids via dysregulation of koebnerisin (S100A15)? A case-control study.

Keloids result from uncontrolled inflammation and fibrosis during wound healing. Vitamin D can regulate skin proliferation and inflammation. Fibroblasts are vitamin D-responsive target cells and are source of koebnerisin (an antimicrobial peptide released during inflammation and wound healing). This study aimed to assess the levels and correlations between the serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin (S100A15) in patients with keloids. Nineteen patients with keloids and 20 matched controls were recruited. From each keloid patient, a serum sample and two biopsies were taken from the keloid (lesional) (Tissue A) and from normal skin (non-lesional) (Tissue B). From controls, a serum sample and a tissue biopsy from normal skin were taken. Serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin were measured in retrieved samples using ELISA. Results revealed a significantly lower serum 25-Hydroxyvitamin D, tissue vitamin D receptors, as well as, serum and tissue koebnerisin in keloid patients compared to controls. Tissue 25-Hydroxyvitamin D was significantly lower in keloidal skin biopsy (Tissue A) compared to non-lesional normal skin biopsy (Tissue B). Tissue koebnerisin showed a significant positive correlation with tissue vitamin D receptors, and a significant negative correlation with tissue 25-Hydroxyvitamin D. There was a significant negative correlation between serum 25-Hydroxyvitamin D and duration of keloid. Accordingly, low serum and tissue 25-Hydroxyvitamin D and deficient tissue vitamin D receptors contribute to the pathogenesis of keloids. This can be partly mediated by dysregulation of the antimicrobial peptide; koebnerisin. Artificial antimicrobial peptides and koebnerisin-modifying drugs, for example, vitamin D and TNF-α inhibitors can have a role in keloid prevention and treatment.

Expression, detection of candidate function and homology modeling for Vicia villosa ornithine δ-aminotransferase.

The accumulation of compatible solutes during stress in plant cell is well documented. Proline is one of these solutes which accumulate in the cytosol in response to drought or salinity stress in plants. Proline has several functions during stress just like osmotic adjustment, osmoprotection, free radical scavenger and antioxidant. Ornithine δ-aminotransferase (δ-OAT) is an important enzyme in proline biosynthetic pathway. It catalyzes the transamination of ornithine to pyrroline-5-carboxylate which can be reduced into proline. Expression of ornithine δ-aminotransferase gene isolated from Vicia villosa (VvOAT) showed protein with a molecular mass of 63 KDa which is compatible with the predicted mass and after VvOAT gene delivery into E. coli host HB101, VvOAT gene enhanced its salt tolerance. Homology modeling of VvOAT was performed based on the crystal structure of the ornithine δ-aminotransferase from humans (PDB code 2OATA). With this model, a flexible docking study with the substrate and inhibitors was performed. The results indicated that PHE170 and ASN171 in VvOAT are the important determinant residues in binding as they have strong hydrogen bonding contacts with the substrate and inhibitors. All the obtained results indicated the efficiency of utilizing this gene in conferring salt tolerance.