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

Abstract

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-κB and production of TNF-α. 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-β1, α-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.

• Authors: Hechang Tan, Jijun Zhao, Shuang Wang, Lili Zhang, Hongyue Wang, Bin Huang, Yingjie Liang, Xueqing Yu, Niansheng Yang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 14 Issue 4 Pg. 401-9 (Dec 2012) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 22922317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Actins
• Antibodies, Antinuclear
• Ccl2 protein, mouse
• Chemokine CCL2
• Fibronectins
• NF-kappa B
• Oligopeptides
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• alpha-smooth muscle actin, mouse
• goralatide

Topics

• Actins (genetics, metabolism)
• Animals
• Antibodies, Antinuclear
• Body Weight
• Chemokine CCL2 (genetics, metabolism)
• Drug Administration Schedule
• Female
• Fibronectins (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Inflammation (drug therapy)
• Kidney (pathology)
• Leukocytes
• Lupus Nephritis (drug therapy, pathology)
• Mice
• Mice, Inbred MRL lpr
• NF-kappa B (genetics, metabolism)
• Oligopeptides (blood, therapeutic use)
• Transforming Growth Factor beta (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)