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The class D scavenger receptor CD68 contributes to mouse chronic liver injury

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Abstract

Scavenger receptors, which are expressed on monocyte/macrophages, play a central role in many pathogenic processes. Here, we examined the role of the class D scavenger receptor (CD68) in bone marrow-derived monocyte/macrophages (BMMs) in chronic liver injury. The expression pattern of multiple scavenger receptors in two liver injury models (methionine-choline-deficient and high fat (MCDHF), carbon tetrachloride (CCl4)) were analyzed by qRT-PCR. CD68 expression was characterized by flow cytometric analysis, immunofluorescence, and qRT-PCR. A selective monocyte/macrophage toxicant, gadolinium chloride (GdCl3) was applied to analyze the function of CD68 in vitro and in vivo. Among the seven examined scavenger receptors (CD68, CD36, CD204, MARCO, LOX1, SREC, and CD163), the mRNA expression of CD68 first got uppermost and continuously increased throughout the entire stage of chronic liver injury, thus attracting our attention. In the injured liver, the percentage of recruited CD68+ BMM increased notably, aligning along the developing fibrotic septa, while the proportion of CD68+ KC stayed the same compared with that of control mice. In vitro CD68 was highly expressed in primary cultured BMM, and CD68 reduction was triggered by macrophage phagocytosis and apoptosis in the presence of GdCl3. In the damaged liver, the recruitment of CD68+ BMM and CD68 mRNA expression were reduced by GdCl3 administration, leading to the attenuation of liver inflammation and fibrosis. Altogether, scavenger receptor CD68 plays a key role in mouse chronic liver injury, which has important implications for the design of anti-fibrotic therapies.

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Funding

This work was supported by grants from the National Natural and Science Foundation of China (81430013, 81670550, 81500465), Beijing Natural Science Foundation (7172019), and the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges Under Beijing Municipality (IDHT20150502).

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Authors and Affiliations

  1. Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, People’s Republic of China

    Le Yang, Lin Yang, Chengbin Dong & Liying Li

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  1. Le Yang
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  2. Lin Yang
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  3. Chengbin Dong
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  4. Liying Li
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Correspondence to Liying Li.

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All animal work was conformed to the Ethics Committee of Capital Medical University and in accordance with the approved guidelines (approval number: AEEI-2014-131).

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The authors declare that they have no conflicts of interest.

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Yang, L., Yang, L., Dong, C. et al. The class D scavenger receptor CD68 contributes to mouse chronic liver injury. Immunol Res 66, 414–424 (2018). https://doi.org/10.1007/s12026-018-9002-y

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