Date: Tuesday, May 5, 2015
Session Name: Poster Session D: Innate Immunity in Transplantation
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Vascular rarefaction is critical in the development of renal fibrosis. Pericytes regulate renal blood flow and might be an important source of renal interstitial myofibroblasts; however little is known on their possible involvement in I/R injury.
Ten pigs underwent to 30min of renal warm I, followed by 24h of R. Five pigs were treated with C1-Inhibitor. Biopsies were analyzed by immunohistochemistry for PDGFRβ. Immunofluorescence(IF) was performed on human pericytes stimulated with C5a for 24h.
I/R injury led to pericyte-myofibroblast trans-differentiation as indicated by a significant reduction in PDGFRβ expression in peritubular capillaries (p<0.05). Pericyte trans-differentiation was associated by alpha-SMA induction, a marker of myofibroblasts without induction of apoptosis (Caspase-3-). Pericyte activation was accompanied by a significant decrease in peritubular capillary lumen area (p<0.05). Interestingly, Complement inhibition preserved PDGFRβ expression (p<0.05), limited alpha-SMA and restored basal capillary area fraction (p<0.05). In accordance, C5a significantly activated pericytes in vitro with down regulation of PDGFRβ (p<0.05), remodeling of αSMA indicating myofibroblasts trans-differentiation (TGF-beta, positive control).
Our study demonstrated that Complement caused pericytes-myofibroblasts trans-differentiation in renal I/R injury with reduction of peritubular capillary area. C1-Inh may be a possible therapeutic strategy to preserve I/R induced vascular rarefaction and myofibroblasts development in transplanted kidney.
To cite this abstract in AMA style:Castellano G, Franzin R, Divella C, Stasi A, Intini A, Gigante M, Lucarelli G, Ditonno P, Battaglia M, Crovace A, Staffieri F, Pertosa G, Oortwijn B, Amersfoort E, Grandaliano G, Gesualdo L. Role of Complement in Mediating Pericyte Trans-Differentiation in Resident Myofibroblasts: A New Hypothesis On Vascular Rarefaction in Renal Ischemia/Reperfusion (I/R) Injury [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/role-of-complement-in-mediating-pericyte-trans-differentiation-in-resident-myofibroblasts-a-new-hypothesis-on-vascular-rarefaction-in-renal-ischemiareperfusion-ir-injury/. Accessed October 31, 2020.
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