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Metabolic remodelling has recently been implicated in other autoimmune diseases; however, its potential role in SSc has received little attention. Here, we aimed to determine whether changes to glycolysis and glutaminolysis are important features of skin fibrosis. TGF\u2010\u03b21, the quintessential pro\u2010fibrotic stimulus, was used to activate fibrotic pathways in NHDFs in vitro. Dermal fibroblasts derived from lesions of SSc patients were also used for in vitro experiments. Parameters of glycolytic function were assessed using by measuring extracellular acidification in response to glycolytic activators\/inhibitors, whilst markers of fibrosis were measured by Western blotting following the use of the glycolysis inhibitors 2\u2010dg and 3PO and the glutaminolysis inhibitor G968. Succinate was also measured after TGF\u2010\u03b21 stimulation. Itaconate was added to SSc fibroblasts and collagen examined. TGF\u2010\u03b21 up\u2010regulates glycolysis in dermal fibroblasts, and inhibition of glycolysis attenuates its pro\u2010fibrotic effects. Furthermore, inhibition of glutamine metabolism also reverses TGF\u2010\u03b21\u2010induced fibrosis, whilst glutaminase expression is up\u2010regulated in dermal fibroblasts derived from SSc patient skin lesions, suggesting that enhanced glutamine metabolism is another aspect of the pro\u2010fibrotic metabolic phenotype in skin fibrosis. TGF\u2010\u03b21 was also able to enhance succinate production, with increased succinate shown to be associated with increased collagen expression. Incubation of SSc cells with itaconate, an important metabolite, reduced collagen expression. TGF\u2010\u03b21 activation of glycolysis is a key feature of the fibrotic phenotype induced by TGF\u2010B1 in skin cells, whilst increased glutaminolysis is also evident in SSc fibroblasts.<\/jats:p>","DOI":"10.1111\/jcmm.16013","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T22:31:40Z","timestamp":1604356300000},"page":"14026-14038","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Metabolic reprogramming of glycolysis and glutamine metabolism are key events in myofibroblast transition in systemic sclerosis pathogenesis"],"prefix":"10.1111","volume":"24","author":[{"given":"John","family":"Henderson","sequence":"first","affiliation":[{"name":"Faculty of Health and Life Sciences Northumbria University Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Duffy","sequence":"additional","affiliation":[{"name":"Faculty of Health 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