Hepatocyte-specific ATG14 deficiency leads to autophagy impairment, hepatomegaly and liver injury under normal dietary conditions. (IMAGE)
Caption
(A) Immunoblot analysis of ATG14, NRF2, SQSTM1 and LC3I/II in the liver of WT and Atg14 HepKO mice (n=4) fed with a chow diet. (B) Serum ALT and AST measurements (n=4–12). (C–I) Body and selected tissue weights in WT and Atg14 HepKO mice fed with a chow diet (n=4–12). (J–L) Blood glucose and hepatic TG and TC measurements in WT and Atg14 HepKO mice fed a chow diet (n=4–12). (M) Macroscopic images, H&E staining and IHC analysis of HNF4α and Ki-67 in the liver of WT and Atg14 HepKO mice (n=4). (N) Immunoblot analysis of Ki-67 and HNF4α in the liver of WT and Atg14 HepKO mice (n=4). (O) IHC analysis of F4/80, Sirius Red staining, Trichrome staining and IF analysis of COL1 in the liver of WT and Atg14 HepKO mice (n=4). (P) Immunoblot analysis of iNOS, TLR4, p-RELA, RELA, and IκBα in the liver of WT and Atg14 HepKO mice (n=4) fed a chow diet. (Q) Real-time PCR analysis of expression of several inflammation-related genes of Tnf, Il6, Il1b, Ccl2, Ccl5 and Il10 in the liver of WT and Atg14 HepKO mice (n=4) fed a chow diet. (R) Immunoblot analysis of COL1, COL3 and ACTA2 in the liver of WT and Atg14 HepKO mice (n=4) fed a chow diet. (S) Real-time PCR analysis of expression of several fibrosis-related genes including Acta2, Col1a1 and Timp1 in the liver of WT and Atg14 HepKO mice (n=4) fed a chow diet. Data were represented by mean±SE. *p<0.05, **p<0.01 and ***p<0.001 for WT versus HepKO. ACTA2, smooth muscle actin alpha 2; ACTN, actinin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATG14, autophagy related 14; BAT, brown adipose tissue; COL1, collagen 1; DAPI, 4′,6-diamidino-2-phenylindole; HepKO, hepatocyte-specific knockout; HNF4α, hepatocyte nuclear factor 4α; IF, immunofluorescence; IHC, immunohistochemistry; IκBα, NF-κB inhibitor α; iNOS, inducible nitric oxide synthase; Ki-67, marker of proliferation Ki-67; LC3, microtubule associated protein 1 light chain 3; NF-κB, nuclear factor kappa B; NRF2, NFE2-related transcription factor 2; p-RELA, phospho-RELA; RELA, RELA proto-oncogene; SQSTM1, sequestosome 1; TC, total cholesterol; TG, triglyceride; Timp1, TIMP metallopeptidase inhibitor 1; TLR4, toll like receptor 4; WAT, white adipose tissue; WT, wildtype.
Credit
By Barry Stein, Jun Wan, Xiaocheng Charlie Dong, et al.
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