Suppressor of Cytokine Signaling-1 Ameliorates Expression of MCP-1 in Diabetic Nephropathy

Background: Janus kinase (JAK)/signal transducers and activators of transcription (STAT) contribute to diabetic nephropathy. Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative feedback regulators of JAK/STAT signaling. This study investigated the effect of SOCS-1 on the JAK/STAT pathway and MCP-1 expression in diabetic nephropathy. Methods: Streptozotocin-induced diabetic mice received pEF-FLAG-I/mSOCS-1 plasmid or pEF-FLAG-I vector for 4 weeks and were compared with age-matched nondiabetic mice. Functional and pathologic markers, expression of monocyte chemoattractant protein-1 (MCP-1) and TGF-beta 1 and phosphorylation of STAT1 and STAT3 were assessed. The effect of SOCS-1 on the expression of MCP-1 in mesangial cells under high glucose conditions was also examined. Results: Urine albumin excretion and renal hypertrophy were alleviated in diabetic mice by overexpression of SOCS-1. The expression of TGF-beta 1 and MCP-1 and the activation of STAT1 and STAT3 were significantly inhibited in diabetic kidney by gene delivery of SOCS-1. In cultured mesangial cells, overexpression of SOCS-1 markedly suppressed high glucose-induced MCP-1 expression. Conclusions: This study suggests that SOCS-1 may attenuate renal damage by ameliorating MCP-1 expression and regulation of the phosphorylation of JAK/STAT in diabetic mice. Copyright (C) 2010 S. Karger AG, Basel