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. 2021 May 25;22(6):e51169. doi: 10.15252/embr.202051169

Figure 7. Overexpressing COUP‐TFII resulted in decreased transcription of PGC1α and PDK4, and knockout of COUP‐TFII increased PGC1α and PDK4 in vitro. Overexpression of PGC1α, however, is not sufficient to suppress TGFβ1‐induced glycolysis and COUP‐TFII induced myofibroblast differentiation.

Figure 7

  1. Volcano plot of all detected proteins from proteomics of TGFβ1‐treated naïve (WT) and COUP‐TFII overexpressing (COUP‐TFII‐OE) cells. PDK4 expression is significantly decreased in OE cells (n = 2).
  2. Without TGFβ treatment, overexpression of COUP‐TFII inhibited, and knockout of COUP‐TFII increased, mRNA of PGC1α. Although overexpression of COUP‐TFII did not change the mRNA of PDK4, knockout of COUP‐TFII significantly increased the expression of PDK4 (n = 6). ***P < 0.001, ****P < 0.0001 by one‐way ANOVA, mean ± SD.
  3. Chip‐qPCR analysis on C3H/10T1/2 cells in vitro revealed binding of COUP‐TFII on the promoter of PGC1α, but not αSMA or PDK4 (n = 2). **P < 0.01, mean ± SD.
  4. Overexpression of PGC1α was achieved through adenovirus transduction in C3H/10T1/2 cells (WT) and confirmed by qRT–PCR (n = 6). ***P < 0.001, ****P < 0.0001 by one‐way ANOVA, mean ± SD.
  5. PGC1α OE significantly increased expression of Cpt1 and PDK4. Both are involved in key steps of FAO. However, overexpression of PGC1α did not abrogate the TGFβ1 up‐regulated glycolytic genes and αSMA (n = 6). *P < 0.05; **P < 0.01; ****P < 0.0001 by one‐way ANOVA, mean ± SD.
  6. PGC1α OE did not decrease αSMA protein neither with nor without TGFβ1 in COUP‐TFII OE cells by Western Blot analysis (n = 3).
  7. Schematic model of the role of COUP‐TFII in metabolic reprogramming during myofibroblast differentiation and fibrosis formation after injury. PDC: pyruvate dehydrogenase complex.