Toll-like receptor 2 agonist exacerbates renal injury in diabetic mice

Inflammation is implicated in the pathogenesis of diabetic nephropathy (DN). Toll-like receptor 2 (TLR2) is a ligand-activated membrane-bound receptor, which induces an inflammatory response, thus serving a crucial role in the pathogenesis of DN. The present study aimed to determine whether a TLR2 agonist, Pam₃CysSK_4, modulates the development of DN. A mouse model of DN was induced using streptozotocin (STZ) and, following the confirmation of hyperglycemia, mice were treated with or without Pam₃CysSK₄. Pathological and functional markers, including the activation of nuclear factor (NF)-κB, expression of TLR2, inflammatory infiltration, myeloid differentiation primary response gene 88 and monocyte chemoattractant protein-1 were assessed. STZ-treated mice exhibited elevated blood glucose levels and increased serum creatinine levels, which increased further following Pam₃CysSK₄ treatment. In addition, Pam₃CysSK₄ treatment was observed to increase podocyte foot process formation. Furthermore, STZ-induced renal glomerular sclerosis was significantly exacerbated in Pam₃CysSK₄-treated mice. Pam₃CysSK₄-treated mice also exhibited increased levels of collagen IV following renal immunostaining, associated with increased macrophage infiltration. Renal expression of TLR2 was markedly elevated in STZ-induced mice; this was further increased in Pam₃CysSK₄-treated mice, accompanied by upregulation of proinflammatory genes and activation of NF-κB. This indicates that enhanced renal expression of TLR2 is associated with inflammatory infiltration in DN and demonstrates that renal injury was exacerbated by the TLR2 agonist in diabetic mice.