Role of Toll-like receptors in diabetic renal lesions in a miniature pig model

• DOI: 10.1126/sciadv.1400183
• Publication Date: 2015-06-23T05:19:08Z
• Authors: Yuanyuan Feng; Shulin Yang; Yuxiang Ma; Xue-Yuan Bai; Xiangmei Chen
• Keywords: TLR3; TRIF; Proinflammatory cytokine; HMGB1

The mechanisms of diabetic renal injury remain unclear. Recent studies have shown that immunological and inflammatory elements play important roles in the initiation development nephropathy (DN). Toll-like receptors (TLRs) comprise a superfamily innate immune system receptors. TLRs pathogenesis lesions are mostly unknown. Compared with rodents, miniature pigs more similar to humans respect metabolism, kidney structure, system, therefore represent an ideal large-animal model for DN mechanistic studies. A diabetes was established by feeding high-sugar high-fat diets. Functional pathological markers, expression activation endogenous TLR ligands [HSP70 (heat shock protein 70) HMGB1], TLR1 TLR11 their downstream signaling pathway molecules (MyD88, IRAK-1, IRF-3), nuclear factor κB (NF-κB) (IKKβ, IκBα, NF-κBp65), cytokines [IL-6 (interleukin-6), MIP-2, MCP-1, CCL5, VCAM-1 (vascular cell adhesion molecule-1)], infiltration cells were systematically evaluated. HSP70 significantly increased pig kidneys. MyD88-dependent TLR2, TLR4, TLR5, TLR7, TLR8, MyD88 phospho-IRAK-1 (activated IRAK-1), as well MyD88-independent TLR3 TLR4 molecule phospho-IRF-3 up-regulated. NF-κB phospho-IKKβ, phospho-IκBα, NF-κBp65, phospho-NF-κBp65 increased. Levels IL-6, VCAM-1, macrophage marker CD68 These results suggested metabolic inflammation activated might role injuries.