Ac-SDKP ameliorates the progression of lupus nephritis in MRL/lpr mice

作者：Tan, Hechang; Zhao, Jijun; Wang, Shuang; Zhang, Lili; Wang, Hongyue; Huang, Bin; Liang, Yingjie; Yu, Xueqing; Yang, Niansheng^*

来源：International Immunopharmacology, 2012, 14(4): 401-409.

DOI：10.1016/j.intimp.2012.07.023

• Lupus nephritis
• Inflammation
• Fibrosis
• Ac-SDKP

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is an endogenous tetrapeptide which can inhibit the differentiation, migration and activation of macrophages and suppress the proliferation of fibroblast. This study examined the effects of Ac-SDKP on the progression of lupus nephritis (LN). MRL/lpr mice received subcutaneous infusion of Ac-SDKP (1.0 mg kg(-1) d(-1)) or vehicle through implanted osmotic mini-pumps from 12 to 20 weeks until being euthanized. MRL/MpJ mice served as normal controls. The data indicative of renal inflammation and fibrosis were evaluated before and after treatment. Ac-SDKP-treated MRL/lpr mice showed reduced proteinuria and improved renal function compared with vehicle-treated controls. Ac-SDKP-treated mice demonstrated decreased inflammatory infiltrates of T cells and macrophages in the kidneys as compared to vehicle-treated animals. The treatment also inhibited the activation of NF-kappa B and production of TNF-alpha. Despite this, immune complex deposition and plasma anti-dsDNA levels were not statistically different between the two groups. In addition, the treatment inhibited renal expression of TGF-beta 1, alpha-SMA and fibronectin as well as the phosphorylation of Smad2/3. Ac-SDKP treatment ameliorated LN through exerting anti-inflammatory and anti-fibrotic effects on MRL/lpr mice, providing therapeutic potential for halting the progression of LN.

• 出版日期2012-12
• 单位中山大学