The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease

Figures

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  Figure 1. RUNX1 is involved in inflammation-mediated NAFLD. Harmful eating habits lead to high levels of circulating triglycerides (TAG), which accumulate in the liver, causing oxidative stress and inflammation. These two processes activate RUNX1, which turns on the angiogenesis pathway to try to repair injuries. At the same time, there is a growth of the adipose tissue that releases free fatty acids (FFA) that reach the liver, leading to lipotoxicity that promotes inflammation. A persistent inflammation state inhibits the tissue remodeling and promotes the release of pro-inflammatory cytokines, which leads to liver tissue damage and enhances the progression of NAFLD to NASH [13,14,15,16,19]. On the other hand, it was also shown that RUNX1 is a positive regulator of TLR4, signaling for the induction of the inflammatory response [21]. TLR are involved in the NAFLD pathogenesis [22].

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  Figure 2. Differential relative mRNA abundance of RUNX1 in liver between (A) women with MO with NL histology and women with MO with NAFLD; (B) women with MO with NL histology, women with MO with SS, and women with MO with NASH. Differential relative mRNA abundance of RUNX1 in the jejunum between (C) women with MO with NL histology and women with MO with NAFLD; (D) women with MO with NL histology, women with MO with SS, and women with MO with NASH. A.U, arbitrary units; MO, morbidly obesity; NAFLD, nonalcoholic fatty liver disease; NL, normal liver; SS, simple steatosis; NASH, nonalcoholic steatohepatitis; RUNX1, runt-related transcription factor 1. p < 0.05 was considered statistically significant (* means p < 0.05; ** means p < 0.01).

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  Figure 3. Representative images of the liver biopsies where the immunohistochemical analysis of RUNX1 was carried out. RUNX1 immunostained images (X400) in (A) normal liver (NL) samples, (B) nonalcoholic steatohepatitis (NASH) samples and (C) simple steatosis (SS) samples. RUNX1 positivity was mostly observed in the nonparenchymal cells. Samples were scored (from one to three) according to the RUNX1 positivity proportion (low or high) and distribution (scattered or clustered). Hematoxylin-stained nuclei were distinguishable from RUNX1-positive brown nuclei. Scale bar: 100 μm.

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  Figure 4. Differential relative mRNA levels of FAS in liver between (A) women with MO with NL histology and women with MO with NAFLD; (B) women with MO with NL histology, women with MO with SS, and women with MO with NASH. Differential relative mRNA levels of TLR9 in the jejunum between (C) women with MO with NL histology and women with MO with NAFLD; (D) women with MO with NL histology, women with MO with SS, and women with MO with NASH. Differential relative mRNA levels of FXR in the jejunum between (E) women with MO with NL histology and women with MO with NAFLD; (F) women with MO with NL histology, women with MO with SS, and women with MO with NASH. A.U, arbitrary units; MO, morbidly obesity; NAFLD, nonalcoholic fatty liver disease; NL, normal liver; SS, simple steatosis; NASH, nonalcoholic steatohepatitis; FAS, fatty acid synthase; TLR, toll-like receptor; FXR, farnesoid X receptor. p < 0.05 was considered statistically significant (* means p < 0.05; ** means p < 0.01; *** means p < 0.001).

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  Figure 5. Role of RUNX1 in gut–liver axis implicated in NAFLD pathogenesis. TAG, triglycerides; RUNX1, runt-related transcription factor 1; TLRs, toll-like receptors; NAFLD, nonalcoholic fatty liver disease; LPS, lipopolysaccharides; PPARγ, peroxisome proliferator-activated receptor gamma; PAMPs, pathogen-associated molecular patterns.

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  Figure 6. Histological images of liver biopsies stained with eosin-hematoxylin from (A) women with MO with NL histology (B) women with MO with SS, and (C) women with MO with NASH. X400, scale bar: 100 μm.