{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:22:07Z","timestamp":1792174927751,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Organ fibrosis, including idiopathic pulmonary fibrosis, is associated with significant morbidity and mortality. Because currently available therapies have limited effect, there is a need to better understand the mechanisms by which organ fibrosis occurs. We have recently reported that transforming growth factor (TGF)-\u03b2, a key cytokine that promotes fibrogenesis, induces the expression of the enzymes of the de novo serine and glycine synthesis pathway in human lung fibroblasts, and that phosphoglycerate dehydrogenase (PHGDH; the first and rate-limiting enzyme of the pathway) is required to promote collagen protein synthesis downstream of TGF-\u03b2. In this study, we investigated whether inhibition of de novo serine and glycine synthesis attenuates lung fibrosis in vivo. We found that TGF-\u03b2 induces mRNA and protein expression of PHGDH in murine fibroblasts. Similarly, intratracheal administration of bleomycin resulted in increased expression of PHGDH in mouse lungs, localized to fibrotic regions. Using a newly developed small molecule inhibitor of PHGDH (NCT-503), we tested whether pharmacologic inhibition of PHGDH could inhibit fibrogenesis both in vitro and in vivo. Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF-\u03b2\u2013induced collagen protein synthesis. Mice treated with the PHGDH inhibitor beginning 7 days after intratracheal instillation of bleomycin had attenuation of lung fibrosis. These results indicate that the de novo serine and glycine synthesis pathway is necessary for TGF-\u03b2\u2013induced collagen synthesis and bleomycin-induced pulmonary fibrosis. PHGDH and other enzymes in the de novo serine and glycine synthesis pathway may be a therapeutic target for treatment of fibrotic diseases, including idiopathic pulmonary fibrosis.<\/jats:p>","DOI":"10.1165\/rcmb.2017-0186oc","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T16:49:10Z","timestamp":1507740550000},"page":"585-593","source":"Crossref","is-referenced-by-count":82,"title":["Inhibition of Phosphoglycerate Dehydrogenase Attenuates Bleomycin-induced Pulmonary Fibrosis"],"prefix":"10.1093","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-356X","authenticated-orcid":false,"given":"Robert B.","family":"Hamanaka","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, Illinois; 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