File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

TitleExtracellular serine empowers epidermal proliferation and psoriasis-like symptoms
Authors
Issue Date2022
Citation
Science Advances, 2022, v. 8, n. 50, article no. abm7902 How to Cite?
AbstractThe 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.
Persistent Identifierhttp://hdl.handle.net/10722/342256
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCappello, Angela-
dc.contributor.authorMancini, Mara-
dc.contributor.authorMadonna, Stefania-
dc.contributor.authorRinaldo, Serena-
dc.contributor.authorPaone, Alessio-
dc.contributor.authorScarponi, Claudia-
dc.contributor.authorBelardo, Antonio-
dc.contributor.authorZolla, Lello-
dc.contributor.authorZuccotti, Alessandro-
dc.contributor.authorPanatta, Emanuele-
dc.contributor.authorPallotta, Sabatino-
dc.contributor.authorAnnicchiarico-Petruzzelli, Margherita-
dc.contributor.authorAlbanesi, Cristina-
dc.contributor.authorCutruzzola, Francesca-
dc.contributor.authorWang, Lu-
dc.contributor.authorJia, Wei-
dc.contributor.authorMelino, Gerry-
dc.contributor.authorCandi, Eleonora-
dc.date.accessioned2024-04-17T07:02:29Z-
dc.date.available2024-04-17T07:02:29Z-
dc.date.issued2022-
dc.identifier.citationScience Advances, 2022, v. 8, n. 50, article no. abm7902-
dc.identifier.urihttp://hdl.handle.net/10722/342256-
dc.description.abstractThe 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.-
dc.languageeng-
dc.relation.ispartofScience Advances-
dc.titleExtracellular serine empowers epidermal proliferation and psoriasis-like symptoms-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/sciadv.abm7902-
dc.identifier.pmid36525488-
dc.identifier.scopuseid_2-s2.0-85144193681-
dc.identifier.volume8-
dc.identifier.issue50-
dc.identifier.spagearticle no. abm7902-
dc.identifier.epagearticle no. abm7902-
dc.identifier.eissn2375-2548-
dc.identifier.isiWOS:000905194200011-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats