Mannan-binding lectin ameliorates renal fibrosis by suppressing macrophage-to-myofibroblast transition

Li Xu; Honglian Jiang; Jingwen Xie; Qishan Xu; Jia Zhou; Xiao Lu; Mingyong Wang; Lijun Dong; Daming Zuo

doi:10.1016/j.heliyon.2023.e21882

Mannan-binding lectin ameliorates renal fibrosis by suppressing macrophage-to-myofibroblast transition

Heliyon. 2023 Nov 8;9(11):e21882. doi: 10.1016/j.heliyon.2023.e21882. eCollection 2023 Nov.

Authors

Li Xu¹, Honglian Jiang^{2

3}, Jingwen Xie⁴, Qishan Xu^{1

4}, Jia Zhou³, Xiao Lu³, Mingyong Wang^{5

6}, Lijun Dong⁷, Daming Zuo⁴

Affiliations

¹ Clinical Research Institute of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, Guangdong Province, 524045, China.
² Department of Laboratory Medicine, Guangzhou First People's Hospital, Guangzhou, Guangdong, 510030, China.
³ Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
⁴ Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, 510515, China.
⁵ Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics, School of Medical Technology, Xinxiang Medical University, Xinxiang, 453003, China.
⁶ School of Medical Technology, Shangqiu Medical College, Shangqiu, 476100, China.
⁷ Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.

Abstract

Mannan-binding lectin (MBL) is a pattern-recognition molecule that plays a crucial role in innate immunity. MBL deficiency correlates with an increased risk of chronic kidney disease (CKD). However, the molecular mechanisms are not fully defined. Here, we established a CKD model in wild-type (WT) and MBL-deficient (MBL^-/-) mice via unilateral ureteral obstruction (UUO). The result showed that MBL deficiency aggravated the pathogenesis of renal fibrosis in CKD mice. Strikingly, the in vivo macrophage depletion investigation revealed that macrophages play an essential role in the MBL-mediated suppression of renal fibrosis. We found that MBL limited the progression of macrophage-to-myofibroblast transition (MMT) in kidney tissues of UUO mice. Further in vitro study showed that MBL^-/- macrophages exhibited significantly increased levels of fibrotic-related molecules compared with WT cells upon transforming growth factor beta (TGF-β) stimulation. We demonstrated that MBL inhibited the MMT process by suppressing the production of matrix metalloproteinase 9 (MMP-9) and activation of Akt signaling. In summary, our study revealed an expected role of MBL on macrophage transition during renal fibrosis, thus offering new insight into the potential of MBL as a therapeutic target for CKD.

Keywords: Macrophages; Mannan-binding lectin; Myofibroblasts; Renal fibrosis.