2. Academic Validation
  3. Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

  • Sci Adv. 2022 Dec 16;8(50):eabm7902. doi: 10.1126/sciadv.abm7902.
Angela Cappello 1 2,  Mara Mancini 2,  Stefania Madonna 2,  Serena Rinaldo 3,  Alessio Paone 3,  Claudia Scarponi 2,  Antonio Belardo 4,  Lello Zolla 4,  Alessandro Zuccotti 2,  Emanuele Panatta 1,  Sabatino Pallotta 2,  Margherita Annicchiarico-Petruzzelli 2,  Cristina Albanesi 2,  Francesca Cutruzzolà 3,  Lu Wang 5,  Wei Jia 5,  Gerry Melino 1,  Eleonora Candi 1 2
Affiliations

Affiliations

  • 1 Department of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
  • 2 Istituto Dermopatico dell'Immacolata, IDI-IRCCS, 00167 Rome, Italy.
  • 3 Department of Biochemical Sciences A.Rossi Fanelli, Sapienza University of Rome, 00185 Rome, Italy.
  • 4 Agriculture and Forest Sciences (DAFNE), University of Tuscia, 01100 Viterbo, Italy.
  • 5 Chinese Medicine and Systems Biology/School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
PMID: 36525488 DOI: 10.1126/sciadv.abm7902
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 tetrahydrofolate-bound 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.

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