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Endothelial to mesenchymal transition and circulating cells contribute to fibroblast formation following renal ischemia reperfusion
Author(s) -
Friedrich Jessica,
Leonard Ellen,
BlazerYost Bonnie,
Basile David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.942.6
Subject(s) - ischemia , population , fibroblast , kidney , pathology , mesenchymal stem cell , renal ischemia , cd31 , medicine , endocrinology , reperfusion injury , chemistry , immunohistochemistry , biology , cell culture , environmental health , genetics
Renal ischemia reperfusion (I/R) results in loss of peritubular capillaries and increased interstitial fibroblasts predisposing chronic kidney disease (CKD). To determine the source of fibroblasts following I/R, male SD rats were subjected to 30 min of bilateral ischemia and reperfusion for 3, 6, 12, 24 hr and 3d, and 7d. S100A4+ immunohistochemistry identified an increase in fibroblasts in the renal cortex within 6 hour relative to sham‐controls (6.5 ±1.1 vs 24.5 ±1.6 cells/field, p < 0.05) and these values remained elevated for the duration of the study. At 6 hours and 24 hours, ~5.8% of S100A4+ cells localized in vascular structures identified using biotinylated tomato lectin infused i.v. just prior to death. In contrast, only ~0.1% of S100A4 cells localized in tubules. Dual immunofluorescence also identified a population of cells defined as S100A4+/CD31+, further suggesting a potential endothelial → mesenchymal transition state. The contribution of circulating cells was evaluated in Lewis rats following a bone marrow transplant with syngenic EGFP rat donors; this resulted in the identification of a population of EGFP+ / S100A4+ cells after renal I/R. Taken together, these data suggest that fibroblast deposition may arise from endothelial and circulating sources following acute renal I/R injury (Support from NIH DK 63114).