Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia

Abstract

Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

Roles of Angiopoietins in Kidney Development and Disease

“…Interestingly, nestin-expressing cells have been located around vasa rectae and, in certain experiments, can participate in angiogenesis, acquiring expression of Tie-2. 65 The observations that some epithelia express Tie genes 12,22,66 should lead to a careful search for these receptors on subsets of renal epithelia, using confocal microscopy and imaging of cilia. If such expression could be established, then it may help to explain some nonendothelial effects observed when angiopoietins are overexpressed.…”

Nestin expression in repopulating mesangial cells promotes their proliferation

“…Earlier studies described nestin as a marker of highly proliferative [36][37][38][39] and migrating cells. 37 In the kidney, a recent study showed nestin-positive cells migrating from the renal papilla to the cortex after ischemia/ reperfusion, 40 indicating a potential role of nestin also for renal cell migration. We found that nestin is a marker that promotes MC proliferation but not migration in vitro.…”

Proliferation and Migration of Label-Retaining Cells of the Kidney Papilla

“…20 Similarly, as in the rat, interstitial cells were markedly more abundant in the base of the papilla than in its tip (data not shown). The H2B-GFP mouse further allowed us to examine several potential markers of the interstitial LRCs, and, stimulated by recent findings, 19 we examined for the presence of nestin; as shown in Figure 7, B and C, we found that the interstitial LRCs were nestin positive.…”

“…Patschan et al 19 reported a population of nestin-positive cells in the kidney papilla that migrates to other parts of the kidney after injury. Because papillary LRCs are present over the whole length of the papilla but proliferate in its upper region and their abundance in the papilla decreases with age, it suggests that the cells upwardly migrate to provide a steady supply of proliferating cells.…”