Platycodin D inhibits the proliferation and migration of hypertrophic scar-derived fibroblasts and promotes apoptosis through a caspase-dependent pathway.

Abstract

Abnormal fibroblast proliferation and excessive extracellular matrix (ECM) deposition lead to the formation of hypertrophic scars (HSs). However, there is no satisfactory method to inhibit the occurrence and development of HSs. In our study, platycodin D (PD), a natural compound extracted from Platycodon grandiflorus, inhibited HSs formation both in vitro and in vivo. First, qRT-PCR and Western blot were used to confirm PD dose-dependently downregulated the expression of Col I, Col III and α-SMA in human hypertrophic scar-derived fibroblasts (HSFs) (p < 0.05). Second, cck-8, transwell and wound healing assays verified PD suppressed the proliferation (p < 0.05) and migration of HSFs (p < 0.05), and inhibited the differentiation of HSFs into myofibroblasts. Moreover, PD-induced HSFs apoptosis were analyzed by flow cytometry and the apoptosis was activated through a caspase-dependent pathway. The rabbit ear scar model was used to further confirm the inhibitory effect of PD on collagen and α-SMA deposition. Finally, Western blot analysis showed that PD reduced TGF-β RI expression (p < 0.05) and affected matrix metalloproteinase 2 (MMP2) protein levels (p < 0.05). In conclusion, our study showed that PD inhibited the proliferation and migration of HSFs by inhibiting fibrosis-related molecules and promoting apoptosis via a caspase-dependent pathway. The TGF-β/Smad pathway also mediated the inhibition of HSFs proliferation and HSFs differentiation into myofibroblasts. Therefore, PD is a potential therapeutic agent for HSs and other fibrotic diseases.

• Authors: Zhencheng Yu, Yun Li, Rao Fu, Yaxin Xue, Danyang Zhao, Dong Han
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 315 Issue 5 Pg. 1257-1267 (Jul 2023) ISSN: 1432-069X [Electronic] Germany
• PMID: 36526799 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• platycodin D
• Matrix Metalloproteinase 2
• Caspases
• Transforming Growth Factor beta

Topics

• Animals
• Humans
• Rabbits
• Cicatrix, Hypertrophic (pathology)
• Matrix Metalloproteinase 2 (metabolism)
• Caspases (metabolism, pharmacology, therapeutic use)
• Fibroblasts
• Apoptosis
• Cell Proliferation
• Transforming Growth Factor beta (metabolism)