title: Toll-like receptor 2 agonist exacerbates renal injury in diabetic mice.
abstract: 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, Pam3CysSK4,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 Pam3CysSK4treatment. In addition, Pam3CysSK4treatment 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.
authors.affiliation: AstraZeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Health Science Center, Shenzhen, Guangdong 518060, P.R. China; Division of Internal Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, Guangdong 518001, P.R. China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Li
authors.affiliation: Division of Internal Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, Guangdong 518001, P.R. China.
authors.forename: Ningyu
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Division of Internal Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, Guangdong 518001, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Internal Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, Guangdong 518001, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Deng
authors.affiliation: Division of Internal Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, Guangdong 518001, P.R. China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: AstraZeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Health Science Center, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
keywords: diabetic nephropathy; inflammation; toll-like receptor 2