APA
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Niğdelioğlu, R., Hamanaka, R., Meliton, A., O'Leary, E., Witt, L., Cho, T., … Mutlu, G. (2016). Transforming Growth Factor (TGF)-β Promotes de Novo Serine Synthesis for Collagen Production*. The Journal of Biological Chemistry.
Chicago/Turabian
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Niğdelioğlu, R., R. Hamanaka, A. Meliton, E. O'Leary, L. Witt, Takugo Cho, Kai Sun, et al. “Transforming Growth Factor (TGF)-β Promotes De Novo Serine Synthesis for Collagen Production*.” The Journal of Biological Chemistry (2016).
MLA
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Niğdelioğlu, R., et al. “Transforming Growth Factor (TGF)-β Promotes De Novo Serine Synthesis for Collagen Production*.” The Journal of Biological Chemistry, 2016.
BibTeX Click to copy
@article{r2016a,
title = {Transforming Growth Factor (TGF)-β Promotes de Novo Serine Synthesis for Collagen Production*},
year = {2016},
journal = {The Journal of Biological Chemistry},
author = {Niğdelioğlu, R. and Hamanaka, R. and Meliton, A. and O'Leary, E. and Witt, L. and Cho, Takugo and Sun, Kai and Bonham, C. and Wu, David and Woods, P. S. and Husain, A. and Wolfgeher, Donald and Dulin, N. and Chandel, N. and Mutlu, G.}
}
TGF-β promotes excessive collagen deposition in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). The amino acid composition of collagen is unique due to its high (33%) glycine content. Here, we report that TGF-β induces expression of glycolytic genes and increases glycolytic flux. TGF-β also induces the expression of the enzymes of the de novo serine synthesis pathway (phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH)) and de novo glycine synthesis (serine hydroxymethyltransferase 2 (SHMT2)). Studies in fibroblasts with genetic attenuation of PHGDH or SHMT2 and pharmacologic inhibition of PHGDH showed that these enzymes are required for collagen synthesis. Furthermore, metabolic labeling experiments demonstrated carbon from glucose incorporated into collagen. Lungs from humans with IPF demonstrated increased expression of PHGDH and SHMT2. These results indicate that the de novo serine synthesis pathway is necessary for TGF-β-induced collagen production and suggest that this pathway may be a therapeutic target for treatment of fibrotic diseases including IPF.
