Fig. 9: Schematic diagram showing the protective function of Trim26 in NASH progression. | Nature Communications

Fig. 9: Schematic diagram showing the protective function of Trim26 in NASH progression.

From: Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPδ signalling activation

Fig. 9: Schematic diagram showing the protective function of Trim26 in NASH progression.The alternative text for this image may have been generated using AI.

Excessive metabolic insults, e.g., western-type diet+15% fructose drinking water (w/v) (WTDF), high fat+high cholesterol diet (HFHC), and 0.5 mM palmitate+1.0 mM oleic acid (PAOA) markedly upregulate Cebpd abundance, subsequently leading to downstream cascade pathway including Hif1a/NF-κB p65/p38 and Nos2 activation. Over-activated Hif1a/NF-κB p65/p38 and Nos2 signalling contributing to increase of lipid deposition, profibrosis- and proinflammation-associated cytokines and chemokines. Thus the proinflammatory and profibrotic factors, e.g., IL-6, IL-1β, TGFβ and TNF-α produced from impaired hepatocytes promote hepatofibrosis development. Conversely, forced increase of Trim26 in hepatocytes significantly block and directly interact with Cebpd to facilitate proteasome-mediated protein degradation, thereafter suppressing Cebpd abundance and its downstream cascade pathway activation.

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