SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells

Dai, Lei, Liu, Yi, Cheng, Lin, Wang, Huiling, Lin, Yi, Shi, Gang, Dong, Zhexu, Li, Junshu, Fan, Ping, Wang, Qinnan
et al (show 10 more authors) (2019) SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells. MUCOSAL IMMUNOLOGY, 12 (5). pp. 1130-1140.

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SARI functions as a suppressor of colon cancer and predicts survival of colon cancer patients, but its role in regulating colitis has not been characterized. Here we show that SARI<sup>-/-</sup> mice were highly susceptible to colitis, which was associated with enhanced macrophage infiltration and inflammatory cytokine production. Bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the deficiency of SARI in the immune compartment but on the protective role of SARI in the intestinal epithelial cells (IECs). Furthermore, SARI deficiency enhanced Chemokine (C-C motif) Ligand 2 (CCL2) production and knockout of CCR2 blocks the promoting role of SARI deficiency on colitis. Mechanistically, SARI directly targets and promotes signal transducer and activator of transcription 1 (STAT1) degradation in IECs, followed by persistent inactivation of the STAT1/CCL2 transcription complex. In summary, SARI attenuated colitis in mice by impairing colitis-dependent STAT1/CCL2 transcriptional activation in IECs and macrophages recruitment in colon tissue.

Item Type: Article
Uncontrolled Keywords: Intestinal Mucosa, Leukocytes, Epithelial Cells, Animals, Mice, Knockout, Mice, Colitis, Disease Models, Animal, Immunohistochemistry, Colonoscopes, STAT1 Transcription Factor, Basic-Leucine Zipper Transcription Factors, Receptors, CCR2, Proteolysis, Biomarkers
Depositing User: Symplectic Admin
Date Deposited: 02 Jul 2019 08:05
Last Modified: 19 Jan 2023 00:39
DOI: 10.1038/s41385-019-0178-9
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