2. Academic Validation
  3. Activation of mannose receptor C type 1 in macrophages improves renal fibrosis through mediating fibronectin endocytosis

Activation of mannose receptor C type 1 in macrophages improves renal fibrosis through mediating fibronectin endocytosis

  • Life Sci. 2025 Jun 15:371:123593. doi: 10.1016/j.lfs.2025.123593.
Luosha Long 1,  Meng Li 2,  Minghui Wang 3,  Baien Liang 2,  Meiying Huang 2,  Xi Yuan 3,  Xinyan Wu 2,  Xiangdong Guo 3,  Suchun Li 4,  Zhende Liu 5,  Weizhi Liu 6,  Wei Chen 4,  Weidong Wang 2,  Qianqian Lyu 7,  Chunling Li 8
Affiliations

Affiliations

  • 1 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Pathology and Pathophysiology, Pu Ai Medical School, Shaoyang University, Shaoyang, China.
  • 2 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 3 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 4 Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Nephrology, National Health Commission and Guangdong Province, Guangzhou, China.
  • 5 Haitang (Jiangsu) Biotechnology Co, Ltd., Nantong, Jiangsu, China.
  • 6 Fang Zongxi Center, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China.
  • 7 Fang Zongxi Center, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China. Electronic address: lyuqianqian@ouc.edu.cn.
  • 8 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address: lichl3@mail.sysu.edu.cn.
PMID: 40164332 DOI: 10.1016/j.lfs.2025.123593
Abstract

Aims: Excess extracellular matrix (ECM) deposition is the characteristic of renal fibrosis, owing to the imbalance between synthesis and degradation. Fibronectin could regulate the deposition of Other ECM, thus plays a crucial role in the progression of renal fibrosis. Mannose Receptor C type 1 (MRC1), largely expressed on macrophages, owns an extracellular fibronectin type II domain that binds to and internalizes Collagen and thus involves in fibrosis modulation. The purpose of the present study was to investigate whether MRC1 participates in the internalization of fibronectin and whether alginate oligosaccharides (AOSC), a degradation product of alginate, has beneficial effects in the resolution of renal fibrosis via MRC1.

Materials and methods: Renal fibrosis models were constructed by unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI) in MRC1-WT and MRC1-KO mice. RAW264.7 cells were treated with TGF-β1 to induce pro-fibrotic responses. Expression of fibrotic markers and fibronectin endocytosis were examined.

Key findings: MRC1 gene knockout aggravated renal fibrosis in UUO and UIRI models. Inhibition of MRC1 exacerbated TGF-β1-induced pro-fibrotic responses in RAW264.7 cells. MRC1 regulated Integrin β1-mediated fibronectin endocytosis through Arp2/3-Kindlin-2 signaling pathway. AOSC improved renal fibrosis by increasing MRC1 expression and endocytosis of fibronectin.

Significance: Our findings highlight the importance of MRC1 and fibronectin endocytosis in the development of renal fibrosis, suggesting that activation of MRC1 by AOSC is probably a therapeutic option to delay the progress of kidney fibrosis.

Keywords

Alginate oligosaccharides; Integrin; Kidney fibrosis; MRC1.

Figures
Products