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| Status |
Public on Dec 07, 2022 |
| Title |
Mechanistic target of rapamycin complex 1 orchestrates the interplay between hepatocytes and Kupffer cells to determine the outcome of immune-mediated hepatitis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The cell-cell interaction between hepatocytes and Kupffer cells (KCs) is crucial for maintaining liver homeostasis, and the loss of KCs and hepatocytes is known to represent a common pathogenic phenomenon in autoimmune hepatitis. Until now, the mechanisms of cell-cell interaction between hepatocytes and KCs involved in immune-mediated hepatitis remains unclear. Here we dissected the impact of activated mTORC1 on the cell-cell interaction of KCs and hepatocyte in immune-mediated hepatitis. In the liver from patients with AIH and mice administrated with Con-A, mTORC1 was activated in both KCs and hepatocytes. The activated mTORC1 signal in hepatocytes with Con-A challenge caused a markedly production of miR-329-3p. Upregulated miR-329-3p inhibited SGMS1 expression in KCs through paracrine, resulting in the death of KCs. Most of maintained KCs were p-S6 positive and distributed in hepatocyte mTORC1 negative area. The activation of mTORC1 enabled KCs expressed complement factor B (CFB) to enhance the complement alternative system, which produced more complement factors to aggravate liver injury. Our findings remonstrate a heterogeneous role of mTORC1 in specific cell type for maintaining tolerogenic liver environment, and will form the basis for the development of new interventions against immune-mediated hepatitis.
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| Overall design |
Total RNA samples were extracted from BMMs of MΦ-Tsc1+/+ or MΦ-Tsc1-/- mice.
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| Contributor(s) |
Sun X, Dai C |
| Citation(s) |
36494334 |
| |
| Submission date |
Nov 24, 2022 |
| Last update date |
Jan 06, 2023 |
| Contact name |
Xiaoli Sun |
| E-mail(s) |
sunxiaoli@njmu.edu.cn
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| Organization name |
2nd Affiliated Hospital, Nanjing Medical University
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| Street address |
262 North Zhongshan Road, Nanjing, Jiangsu
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| City |
Nanjing |
| ZIP/Postal code |
210000 |
| Country |
China |
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| Platforms (1) |
| GPL22782 |
Agilent-074512 CBCmouselncRNAmRNA180k |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA904947 |
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