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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.

Titel:	Ac-SDKP ameliorates the progression of lupus nephritis in MRL/lpr mice.
Autor/in / Beteiligte Person:	Tan, H ; Zhao, J ; Wang, S ; Zhang, L ; Wang, H ; Huang, B ; Liang, Y ; Yu, X ; Yang, N
Link:	Zum Volltext
Zeitschrift:	International immunopharmacology, Jg. 14 (2012-12-01), Heft 4, S. 401
Veröffentlichung:	Amsterdam ; New York : Elsevier Science, c2001-, 2012
Medientyp:	academicJournal
ISSN:	1878-1705 (electronic)
DOI:	10.1016/j.intimp.2012.07.023
Schlagwort:	Actins genetics Actins metabolism Animals Antibodies, Antinuclear Body Weight Chemokine CCL2 genetics Chemokine CCL2 metabolism Drug Administration Schedule Female Fibronectins genetics Fibronectins metabolism Gene Expression Regulation drug effects Inflammation drug therapy Kidney pathology Leukocytes Lupus Nephritis pathology Mice Mice, Inbred MRL lpr NF-kappa B genetics NF-kappa B metabolism Oligopeptides blood Transforming Growth Factor beta genetics Transforming Growth Factor beta metabolism Tumor Necrosis Factor-alpha genetics Tumor Necrosis Factor-alpha metabolism Lupus Nephritis drug therapy Oligopeptides therapeutic use
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Int Immunopharmacol] 2012 Dec; Vol. 14 (4), pp. 401-9. <i>Date of Electronic Publication: </i>2012 Aug 24. MeSH Terms: Lupus Nephritis / drug therapy ; Oligopeptides / therapeutic use ; Actins / genetics ; Actins / metabolism ; Animals ; Antibodies, Antinuclear ; Body Weight ; Chemokine CCL2 / genetics ; Chemokine CCL2 / metabolism ; Drug Administration Schedule ; Female ; Fibronectins / genetics ; Fibronectins / metabolism ; Gene Expression Regulation / drug effects ; Inflammation / drug therapy ; Kidney / pathology ; Leukocytes ; Lupus Nephritis / pathology ; Mice ; Mice, Inbred MRL lpr ; NF-kappa B / genetics ; NF-kappa B / metabolism ; Oligopeptides / blood ; Transforming Growth Factor beta / genetics ; Transforming Growth Factor beta / metabolism ; Tumor Necrosis Factor-alpha / genetics ; Tumor Necrosis Factor-alpha / metabolism Substance Nomenclature: 0 (Actins) ; 0 (Antibodies, Antinuclear) ; 0 (Ccl2 protein, mouse) ; 0 (Chemokine CCL2) ; 0 (Fibronectins) ; 0 (NF-kappa B) ; 0 (Oligopeptides) ; 0 (Transforming Growth Factor beta) ; 0 (Tumor Necrosis Factor-alpha) ; 0 (alpha-smooth muscle actin, mouse) ; H041538E9P (goralatide) Entry Date(s): Date Created: 20120828 Date Completed: 20130604 Latest Revision: 20121203 Update Code: 20240513

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