title: 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.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Hechang
authors.initials: H
authors.lastname: Tan
authors.forename: Jijun
authors.initials: J
authors.lastname: Zhao
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Hongyue
authors.initials: H
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Liang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.forename: Niansheng
authors.initials: N
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000974:Antibodies, Antinuclear; D001835:Body Weight; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D007668:Kidney / Q000473:pathology; D007962:Leukocytes; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000097:blood / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000974:Antibodies, Antinuclear; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005353:Fibronectins; D016328:NF-kappa B; D009842:Oligopeptides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C544013:alpha-smooth muscle actin, mouse; C058504:goralatide