Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

Angela Cappello, Mara Mancini, Stefania Madonna, Serena Rinaldo, Alessio Paone, Claudia Scarponi, Antonio Belardo, Lello Zolla, Alessandro Zuccotti, Emanuele Panatta, Sabatino Pallotta, Margherita Annicchiarico-Petruzzelli, Cristina Albanesi, Francesca Cutruzzola, Lu Wang, Wei Jia, Gerry Melino, Eleonora Candi*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

6 Citations (Scopus)

Abstract

The contribution of nutrient availability to control epidermal cell proliferation, inflammation, and hyperproliferative diseases remains unknown. Here, we studied extracellular serine and serine/glycine metabolism using human keratinocytes, human skin biopsies, and a mouse model of psoriasis-like disease. We focused on a metabolic enzyme, serine hydroxymethyltransferase (SHMT), that converts serine into glycine and tetrahydrofolatebound one-carbon units to support cell growth. We found that keratinocytes are both serine and glycine auxotrophs. Metabolomic profiling and hypoxanthine supplementation indicated that SHMT silencing/inhibition reduced cell growth through purine depletion, leading to nucleotide loss. In addition, topical application of an SHMT inhibitor suppressed both keratinocyte proliferation and inflammation in the imiquimod model and resulted in a decrease in psoriasis-associated gene expression. In conclusion, our study highlights SHMT2 activity and serine/glycine availability as an important metabolic hub controlling both keratinocyte proliferation and inflammatory cell expansion in psoriasis and holds promise for additional approaches to treat skin diseases.

Original languageEnglish
Article numberabm7902
Number of pages17
JournalScience advances
Volume8
Issue number50
Early online date16 Dec 2022
DOIs
Publication statusPublished - Dec 2022

Scopus Subject Areas

  • General

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