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Fig. 5 | Journal of Hematology & Oncology

Fig. 5

From: Hepatic NOD2 promotes hepatocarcinogenesis via a RIP2-mediated proinflammatory response and a novel nuclear autophagy-mediated DNA damage mechanism

Fig. 5

NOD2 interacts with lamin A/C and promotes its degradation through nuclear autophagy. a Co-immunoprecipitation of endogenous NOD2 with lamin A/C in primary hepatocytes. b GST pull-down assay showing that NOD2 directly interacts with lamin A/C through its LRR domain (amino acids 619–1040). c Immunofluorescence showed co-localization (yellow) of HA-NOD2 (green) and lamin A/C (red) in primary hepatocytes after MDP treatment. Bar graphs shown are HA-NOD2 nuclear translocation ratio and overlap co-efficient of HA-NOD2/lamin A/C co-localization, n = 3; *P < 0.05. Scale bar, 5 μm. d NOD2 activation decreases lamin A/C protein independently from RIP2. Primary hepatocytes from indicated mice were treated with different concentrations of MDP for 4 h or MDP (10 μg/ml) at the indicated time points. e Primary hepatocytes were treated with MDP (10 μg/ml), and then, p-RIP2, lamin A/C, LC3 and P62 protein levels were examined in the nucleus and cytoplasm. f Primary hepatocytes from indicated mice were treated with MDP (10 μg/ml). The protein levels of lamin A/C, LC3 and P62 were examined in the nucleus. g Transmission electron microscopy analysis of primary hepatocytes treated with MDP. White arrow: autophagosome; black arrow: perinuclear heterochromatin; representative nuclear membrane collapse and perinuclear heterochromatin decrease are labeled as event 1 and event 2, respectively. Nu, nucleus. Scale bar, 2.5 μm or 500 nm. h Primary hepatocytes expressing HA-NOD2 were infected with lentivirus carrying GFP-LC3 and treated with vehicle or MDP (10 μg/ml) for 2 h. Cells were then stained with lamin A/C and HA antibodies. co-localization (white) of lamin A/C (red), HA-NOD2 (purple), GFP-LC3 (green) and DAPI (blue) in primary hepatocytes was imaged by confocal microscopy after MDP treatment. Nuclear and cytoplasmic events are indicated by arrows. Scale bar, 5 μm. Data were shown as mean ± SD, and significance was determined using Student’s t test (c)

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