ArticleScientific reports2019
Attenuated Lymphatic Proliferation Ameliorates Diabetic Nephropathy and High-Fat Diet-Induced Renal Lipotoxicity.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of diabetic kidney disease (DKD).Cell death discovery · 2026Review
- Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy.Renal failure · 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
- Microglia Promote Lymphangiogenesis Around the Spinal Cord Through VEGF-C/VEGFR3-Dependent Autophagy and Polarization After Acute Spinal Cord Injury.Molecular neurobiology · 2025Article
- Expression Profile of Urinary Exosomal miRNAs in Patients With Diabetic Kidney Disease and Their Association With Kidney Damage.International journal of endocrinology · 2025Article
- The immune regulatory role of lymphangiogenesis in kidney disease.Journal of translational medicine · 2024Review
- Acute kidney injury results in long-term alterations of kidney lymphatics in mice.American journal of physiology. Renal physiology · 2024Article
- Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- LncTUG1 ameliorates renal tubular fibrosis in experimental diabetic nephropathy through the miR-145-5p/dual-specificity phosphatase 6 axis.Renal failure · 2023Article
- Angiogenesis-An Emerging Role in Organ Fibrosis.International journal of molecular sciences · 2023Review
- The association between dietary micronutrient patterns and odds of diabetic nephropathy: A case-control study.Food science & nutrition · 2023Article
- Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.International journal of molecular sciences · 2023Article
- The role of cellular crosstalk in the progression of diabetic nephropathy.Frontiers in endocrinology · 2023Review
- Pathological Connections between Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease.Kidney diseases (Basel, Switzerland) · 2022Review
- Lymphangiogenesis and Lymphatic Barrier Dysfunction in Renal Fibrosis.International journal of molecular sciences · 2022Review
- Roles and crosstalks of macrophages in diabetic nephropathy.Frontiers in immunology · 2022Review
- The lymphatics in kidney health and disease.Nature reviews. Nephrology · 2021Review
- Integrated metabolomics coupled with pattern recognition and pathway analysis to reveal molecular mechanism of cadmium-induced diabetic nephropathy.Toxicology research · 2021Article
- Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization.Cell death & disease · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymphangiogenesis occurs in response to renal injury and is correlated with interstitial fibrosis. Diabetes- and high-fat diet (HFD)-induced intrarenal lipotoxicity and their relationships with lymphangiogenesis are not established. We used PPARα agonist, fenofibrate, to unravel the linkage between lipotoxicity and lymphangiogenesis. Eight-week-old male C57BLKS/J db/db mice and HFD Spontaneously hypertensive rats (SHRs) were fed fenofibrate for 12 weeks. HK-2 and RAW264.7 cells were used to investigate their lymphangiogenic capacity in relation to lipotoxicity. Fenofibrate improved intrarenal lipotoxicity by increasing expression of PPARα and phosphorylation of AMPK. Lymphatic proliferation was attenuated; expression of lymphatic endothelial hyaluronan receptor-1 (LYVE-1), podoplanin, vascular endothelial growth factor-C (VEGF-C), and vascular endothelial growth factor receptor-3 (VEGFR-3) was decreased. In parallel, extent of tubulointerstitial fibrosis, apoptosis and inflammatory cell infiltration was reduced. In HK2 cells, palmitate- and high glucose-induced over expression of lymphatic makers was diminished by fenofibrate via activation of PPARα-AMPK-pACC signaling. Enhanced expression of M1 phenotype in RAW264.7 cells correlated with increased lymphatic growth. A causal relationship between lipotoxicity and lymphatic proliferation with a cellular link to macrophage activation can be speculated; pro-inflammatory M1 type macrophage is involved in the development of lymphangiogenesis through stimulation of VEGF-C and by its transdifferentiation into lymphatic endothelial cells.
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