Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway

Jinpeng Lv; Xiaohong An; Songzhou Jiang; Ying Yang; Guoqiang Song; Rongyin Gao

doi:10.3389/fphar.2020.569368

Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway

Front Pharmacol. 2020 Sep 11:11:569368. doi: 10.3389/fphar.2020.569368. eCollection 2020.

Authors

Jinpeng Lv¹, Xiaohong An², Songzhou Jiang¹, Ying Yang¹, Guoqiang Song¹, Rongyin Gao³

Affiliations

¹ Department of Pharmacy, College of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, China.
² Shanghai Jiyan Bio-pharmaceutical Co., Ltd., Shanghai, China.
³ Department of Pharmacy, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Abstract

Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesis-stimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3', 5'-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.

Keywords: 5’-monophosphate/protein kinase G; cyclic guanosine 3’; guanylate cyclase; melanogenesis; melanosome transport; protoporphyrin IX.