2. Academic Validation
  3. Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis

Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis

  • Cell Mol Immunol. 2024 Jun 13. doi: 10.1038/s41423-024-01190-6.
Qing Ouyang # 1,  Chao Wang # 2 3,  Tian Sang # 2,  Yan Tong # 2,  Jian Zhang 2,  Yulan Chen 2,  Xue Wang 2,  Lingling Wu 2,  Xu Wang 2,  Ran Liu 2,  Pu Chen 2,  Jiaona Liu 2,  Wanjun Shen 2,  Zhe Feng 2,  Li Zhang 2,  Xuefeng Sun 2,  Guangyan Cai 4,  Li-Li Li 5,  Xiangmei Chen 6
Affiliations

Affiliations

  • 1 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China. nolimithyer3169@outlook.com.
  • 2 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China.
  • 3 Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 4 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China. caiguangyan@sina.com.
  • 5 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, 100190, China. lill@nanoctr.cn.
  • 6 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China. xmchen301@126.com.
  • # Contributed equally.
PMID: 38871810 DOI: 10.1038/s41423-024-01190-6
Abstract

Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys. Renal fibrosis involves an immune response dominated by macrophages, which activates myofibroblasts in fibrotic niches. However, macrophages exhibit high heterogeneity, hindering their potential as therapeutic cell targets. Herein, we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially. We identified the major profibrotic macrophage subset (Fn1+Spp1+Arg1+) in the kidney and then constructed a 12-mer Glycopeptide that was designated as bioactivated in vivo assembly PK (BIVA-PK) to deplete these cells. BIVA-PK specifically binds to and is internalized by profibrotic macrophages. By inducing macrophage cell death, BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses. The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.

Keywords

Bioactivated in vivo assembly-PK (BIVA-PK); Renal fibrosis; cell death; immune microenvironment; pro-fibrotic macrophage.

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