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.

Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms / Cappello, Angela; Mancini, Mara; Madonna, Stefania; Rinaldo, Serena; Paone, Alessio; Scarponi, Claudia; Belardo, Antonio; Zolla, Lello; Zuccotti, Alessandro; Panatta, Emanuele; Pallotta, Sabatino; Annicchiarico-Petruzzelli, Margherita; Albanesi, Cristina; Cutruzzola', Francesca; Wang, Lu; Jia, Wei; Melino, Gerry; Candi, Eleonora. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 8:50(2022). [10.1126/sciadv.abm7902]

Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

Rinaldo, Serena;Paone, Alessio;Cutruzzola', Francesca;
2022

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.
2022
metabolism; serine; keratinocytes
01 Pubblicazione su rivista::01a Articolo in rivista
Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms / Cappello, Angela; Mancini, Mara; Madonna, Stefania; Rinaldo, Serena; Paone, Alessio; Scarponi, Claudia; Belardo, Antonio; Zolla, Lello; Zuccotti, Alessandro; Panatta, Emanuele; Pallotta, Sabatino; Annicchiarico-Petruzzelli, Margherita; Albanesi, Cristina; Cutruzzola', Francesca; Wang, Lu; Jia, Wei; Melino, Gerry; Candi, Eleonora. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 8:50(2022). [10.1126/sciadv.abm7902]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1666833
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