title: Dermatan sulfate reduces monocyte chemoattractant protein 1 and TGF-β production, as well as macrophage recruitment and myofibroblast accumulation in mice with unilateral ureteral obstruction.
abstract: Selectins play an essential role in most inflammatory reactions, mediating the initial leukocyte-rolling event on activated endothelium. Heparin and dermatan sulfate (DS) bind and block P- and L-selectin function in vitro. Recently, we reported that subcutaneous administration of DS inhibits colon inflammation in rats by reducing macrophage and T-cell recruitment and macrophage activation. In the present study, we examined the effect of porcine intestinal mucosa DS on renal inflammation and fibrosis in mice after unilateral ureteral obstruction (UUO). Twenty-four adult male Swiss mice weighing 20-25 g were divided into 4 groups: group C (N = 6) was not subjected to any surgical manipulation; group SH (N = 6) was subjected to surgical manipulation but without ureter ligation; group UUO (N = 6) was subjected to unilateral ureteral obstruction and received no treatment; group UUO plus DS (N = 6) was subjected to UUO and received DS (4 mg/kg) subcutaneously daily for 14 days. An immunoblot study was also performed for TGF-β. Collagen (stained area ~3700 µm(2)), MCP-1 (stained area ~1700 µm(2)), TGF-β (stained area ~13% of total area), macrophage (number of cells ~40), and myofibroblast (stained area ~1900 µm(2)) levels were significantly (P < 0.05) higher in the UUO group compared to control. DS treatment significantly (P < 0.05) reduced the content of collagen (stained area ~700 µm(2)), MCP-1 (stained area ~160 µm(2)) and TGF-β (stained area ~5% of total area), in addition to myofibroblast (stained area ~190 µm(2)) and macrophage (number of cells ~32) accumulation in the obstructed kidney. Overall, these results indicate that DS attenuates kidney inflammation by reducing macrophage recruitment, myofibroblast population and fibrosis in mice submitted to UUO.
authors.affiliation: Laboratório de Bioquímica e Biologia Celular de Glicoconjugados, Programa de Glicobiologia, Instituto de Bioquímica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brasil.
authors.forename: C L R
authors.initials: CL
authors.lastname: Belmiro
authors.forename: R G
authors.initials: RG
authors.lastname: Gonçalves
authors.forename: E O
authors.initials: EO
authors.lastname: Kozlowski
authors.forename: A F
authors.initials: AF
authors.lastname: Werneck
authors.forename: C M
authors.initials: CM
authors.lastname: Takyia
authors.forename: M
authors.initials: M
authors.lastname: Leite
authors.forename: M S G
authors.initials: MS
authors.lastname: Pavão
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005355:Fibrosis; D007279:Injections, Subcutaneous; D007668:Kidney / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism; D009393:Nephritis / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014517:Ureteral Obstruction / Q000150:complications* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D016212:Transforming Growth Factor beta; D003871:Dermatan Sulfate