ArticleCell death & disease2021
Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Lymphangiogenesis in hypercholesterolemic skin: A comparative study of xanthomatous and non-xanthomatous lesions.JID innovations : skin science from molecules to population health · 2026Article
- Esaxerenone Attenuates Aldosterone-Induced Renal Fibrosis by Suppressing Fibroblast-to-Lymphatic Endothelial-like Cell Transdifferentiation.International journal of molecular sciences · 2026Article
- NF-κB-driven lymphangiogenesis affects kidney function via a VEGFR-3-mediated pathway.JCI insight · 2026Article
- The role of the vascular niche in regulating kidney tubulointerstitial fibrosis.Kidney international · 2026Review
- Article
- Inflammatory bowel disease and renal disorders: from clinical associations to shared mechanisms and management strategies.Frontiers in immunology · 2026Review
- Lymphatic Endothelial Cells and Organ-Associated Lymphangiogenesis in Tumor Microenvironment.Cells · 2025Review
- Moving toward a better understanding of renal lymphatics: challenges and opportunities.Pediatric nephrology (Berlin, Germany) · 2025Review
- Adrenomedullin production by adult cardiac fibroblasts via NF-κB/STAT6 signaling enhances post-infarction lymphangiogenesis and cardiac repair.Scientific reports · 2025Article
- Aldosterone induces renal lymphangiogenesis through macrophage-lymphatic endothelial cell transformation and Inhibition by esaxerenone.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- Microglia Promote Lymphangiogenesis Around the Spinal Cord Through VEGF-C/VEGFR3-Dependent Autophagy and Polarization After Acute Spinal Cord Injury.Molecular neurobiology · 2025Article
- SIX1 aggravates the progression of spinal cord injury in mice by promoting M1 polarization of microglia.Scientific reports · 2025Article
- The MIR181A2HG/miR-5680/VCAN-CD44 Axis Regulates Gastric Cancer Lymph Node Metastasis by Promoting M2 Macrophage Polarization.Cancer medicine · 2025Article
- Neutrophils in tumor- and inflammation-induced lymphangiogenesis.International journal of biological sciences · 2025Review
- Therapeutic potential of formononetin in cirrhotic portal hypertension: modulating hepatic fibrosis, macrophage polarization, and lymphangiogenesis.Frontiers in immunology · 2025Article
- The multifaceted role of macrophages in kidney physiology and diseases.Frontiers in immunology · 2025Review
- Voluntary wheel running promotes lymphangiogenesis in slow-twitch muscle in young mice.Frontiers in physiology · 2025Article
- Targeting tumor-draining lymph node to overcome resistance to cancer immunotherapy: an update.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- VEGFC Overexpression in Kidney Progenitor Cells Is a Model of Renal Lymphangiectasia-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation plays a crucial role in the occurrence and development of renal fibrosis, which ultimately results in end-stage renal disease (ESRD). There is new focus on lymphangiogenesis in the field of inflammation. Recent studies have revealed the association between lymphangiogenesis and renal fibrosis, but the source of lymphatic endothelial cells (LECs) is not clear. It has also been reported that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms in other tissues. We hypothesized that there was a close relationship between macrophages and lymphatic endothelial progenitor cells in renal fibrosis. In this study, we demonstrated that lymphangiogenesis occurred in a renal fibrosis model and was positively correlated with the degree of fibrosis and macrophage infiltration. Compared to resting (M0) macrophages and alternatively activated (M2) macrophages, classically activated (M1) macrophages predominantly transdifferentiated into LECs in vivo and in vitro. VEGF-C further increased M1 macrophage polarization and transdifferentiation into LECs by activating VEGFR3. It was suggested that VEGF-C/VEGFR3 pathway activation downregulated macrophage autophagy and subsequently regulated macrophage phenotype. The induction of autophagy in macrophages by rapamycin decreased M1 macrophage polarization and differentiation into LECs. These results suggested that M1 macrophages promoted lymphangiogenesis and contributed to newly formed lymphatic vessels in the renal fibrosis microenvironment, and VEGF-C/VEGFR3 signaling promoted macrophage M1 polarization by suppressing macrophage autophagy and then increased the transdifferentiation of M1 macrophages into LECs.
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