# A Marine-Derived Steroid from Rhodococcus sp., 3,12-Dioxochola-4,6-dien-24-oic Acid, Enhances Skin Re-Epithelialization and Tissue Repair

## TL;DR

A new marine-derived steroid compound, DOCDA, was found to speed up wound healing by boosting cell movement and activating regenerative signals in skin cells.

## Contribution

The discovery of DOCDA as a novel marine-derived steroid that promotes wound healing through activation of regenerative signaling and stem-like properties.

## Key findings

- DOCDA promotes wound healing by enhancing HaCaT cell invasion and migration and upregulating growth factors like EGF and VEGF-A.
- DOCDA increases expression of genes related to focal adhesion and cytoskeletal regulation, such as ITGB1, FAK, and RHOA.
- Topical application of DOCDA in mice resulted in over 70% wound closure within 5 days.

## Abstract

The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of −7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy.