ArticleScience advances2015
Role of Toll-like receptors in diabetic renal lesions in a miniature pig model.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Molecular Pathogenesis of Avian Splenic Injury Under Thermal Challenge: Integrated Mitigation Strategies for Poultry Heat Stress.Current issues in molecular biology · 2025Review
- Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers' Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway.Biological trace element research · 2025Article
- Exacerbation of diabetes due to F. Nucleatum LPS-induced SGLT2 overexpression in the renal proximal tubular epithelial cells.BMC nephrology · 2025Article
- The Role of Gender Differences and Menopause in Obesity-Related Renal Disease, Renal Inflammation and Lipotoxicity.International journal of molecular sciences · 2023Article
- Integrated Analysis of Single-Cell RNA-Seq and Bulk RNA-Seq Combined with Multiple Machine Learning Identified a Novel Immune Signature in Diabetic Nephropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- From Diabetic Nephropathy to End-Stage Renal Disease: The Effect of Chemokines on the Immune System.Journal of diabetes research · 2023Article
- Ginsenoside Compound K Ameliorates Development of Diabetic Kidney Disease through Inhibiting TLR4 Activation Induced by Microbially Produced Imidazole Propionate.International journal of molecular sciences · 2022Article
- Targeting inflammation for the treatment of Diabetic Kidney Disease: a five-compartment mechanistic model.BMC nephrology · 2022Review
- Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model.BMC nephrology · 2021Article
- Insulin-Mimic Components inPharmaceuticals (Basel, Switzerland) · 2021Article
- Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs.Science advances · 2021Article
- Advances in understanding the innate immune-associated diabetic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Review
- Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection.BMC immunology · 2021Article
- Immunohistochemical study for the expression of leukocyte adhesion molecules, and FGF23 and ACE2 in P. gingivalis LPS-induced diabetic nephropathy.BMC nephrology · 2021Article
- Toll-Like Receptors Regulate the Development and Progression of Renal Diseases.Kidney diseases (Basel, Switzerland) · 2021Review
- TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy.JCI insight · 2020Article
- Dietary resveratrol supplementation inhibits heat stress-induced high-activated innate immunity and inflammatory response in spleen of yellow-feather broilers.Poultry science · 2019Article
- Regulation and Molecular Mechanism ofAnimals : an open access journal from MDPI · 2019Article
- 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione isolated fromDiabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- miR-374a Regulates Inflammatory Response in Diabetic Nephropathy by Targeting MCP-1 Expression.Frontiers in pharmacology · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms of diabetic renal injury remain unclear. Recent studies have shown that immunological and inflammatory elements play important roles in the initiation and development of diabetic nephropathy (DN). Toll-like receptors (TLRs) comprise a superfamily of innate immune system receptors. The roles and mechanisms of TLRs in the pathogenesis of diabetic renal lesions are mostly unknown. Compared with rodents, miniature pigs are more similar to humans with respect to metabolism, kidney structure, and immune system, and therefore represent an ideal large-animal model for DN mechanistic studies. A diabetes model was established by feeding miniature pigs with high-sugar and high-fat diets. Functional and pathological markers, expression and activation of endogenous TLR ligands [HSP70 (heat shock protein 70) and HMGB1], TLR1 to TLR11 and their downstream signaling pathway molecules (MyD88, IRAK-1, and IRF-3), nuclear factor κB (NF-κB) signaling pathway molecules (IKKβ, IκBα, and NF-κBp65), inflammatory cytokines [IL-6 (interleukin-6), MIP-2, MCP-1, CCL5, and VCAM-1 (vascular cell adhesion molecule-1)], and infiltration of inflammatory cells were systematically evaluated. The expression of HSP70 was significantly increased in diabetic pig kidneys. The expression of MyD88-dependent TLR2, TLR4, TLR5, TLR7, TLR8, and TLR11 and their downstream signaling molecules MyD88 and phospho-IRAK-1 (activated IRAK-1), as well as that of MyD88-independent TLR3 and TLR4 and their downstream signaling molecule phospho-IRF-3 (activated IRF-3), was significantly up-regulated. The expression and activation of NF-κB pathway molecules phospho-IKKβ, phospho-IκBα, NF-κBp65, and phospho-NF-κBp65 were significantly increased. Levels of IL-6, MIP-2, MCP-1, CCL5, VCAM-1, and macrophage marker CD68 were significantly increased in diabetic pig kidneys. These results suggested that the metabolic inflammation activated by TLRs might play an important role in diabetic renal injuries.
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