Effect of SOCS1 on diabetic renal injury through regulating TLR signaling pathway.

Abstract

To clarify the effect of suppressor of cytokine signaling 1 (SOCS1) on diabetic nephropathy (DN)-induced renal injury by regulating the Toll-like receptor (TLR) signaling pathway. The Sprague-Dawley rats were divided into control group (n=10) and DN group (established with streptozotocin injection, n=20). The DN rats were administrated with SOCS1 lentivirus to upregulate the in vivo expression. The rat blood glucose was detected to confirm the successful preparation of the DN model. The hepatic and renal function indexes, including blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and creatinine (CR) were detected. The pathological lesions in the kidney were observed via hematoxylin-eosin (HE) staining. Besides, the serum levels of the inflammatory factors in rats were detected via enzyme-linked immunosorbent assay (ELISA). The relative levels of genes in the TLR signaling pathway were detected via RT-PCR and Western blotting. The blood glucose level in rats of the DN group was significantly enhanced, indicating the successful modeling. The expression of SOCS1 was significantly upregulated in rats administrated with SOCS1 lentivirus. The contents of BUN, ALP, ALT, and CR in rats of SOCS1 overexpression group were significantly lower than those in the DN group. The inflammatory infiltration in the kidney and the glomerular injury were pronounced in the DN group. The serum levels of interleukin-1 (IL-1), interferon-γ (INF-γ), and tumor necrosis factor-α (TNF-α) were significantly declined in SOCS1 overexpression group. Besides, the mRNA expressions of myeloid differential protein-88 (MyD88), TLR2, and INF-γ, and the protein expression of TLR2 were all remarkably downregulated in SOCS1 overexpression group. SOCS1 can promote renal injury repair in DN rats by inhibiting the TLR pathway. Therefore, SOCS1 is expected to be a new target for the repair of DN renal injury.