This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes) during regeneration of S3 tubules of outer stripe of outer medulla (OSOM). Groups of experimental animals (n = 4) were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU) and Proliferating Cell Nuclear Antigen (PCNA) labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM) positive interstitial cells increased transiently (18–72 hours) in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA)-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.
Our data suggest that positive cells (BrdU(+), CD44(+), vimentin(+) and CD45(-)) observed in kidney tubules after ischaemia could originate from an extrarenal source and reach the renal parenchyma via blood vessels. We postulate that these immature cells migrate to injured tubules, proliferate and finally differentiate into mature epithelial cells leading to the replacement of a majority (>80%) of altered S3 cells.
Aims: We used a rat model of renal ischemia (35 min) to test the potential involvement of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in the process of S3 tubule regeneration. Methods: A monoclonal antibody specific for murine PECAM-1 was injected i.p. immediately after kidney reperfusion or 48 h post-ischemia. One day before ischemia, each animal received an i.p. injection of 80 mg/kg 5-bromo-2′-deoxyuridine (BrdU). Experimental animals were sacrificed 1, 2, 3, 7 and 14 days post-ischemia. Renal sections were processed to characterize the histopathological alterations and the distribution of BrdU-immunopositive cells. Results: Our observations showed that anti-PECAM-1 administration was associated with an inhibition of S3 tubule regeneration along with a progressive cystic dilatation of renal tubules that was particularly prominent 2 weeks post-ischemia. Interestingly, injection of anti-PECAM-1 48 h post-ischemia failed to block renal regeneration and was followed by a normal re-epithelialization of S3 tubules. Conclusion: Our data showed that the blockade of PECAM-1 immediately after kidney reperfusion inhibits tubular regeneration. These observations suggest that transendothelial migration of extrarenal cells could be a precocious and pivotal step in kidney reparation, but also suggest that these extrarenal cells could be essential to the process of tubular regeneration.
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