Label-retaining cells in the kidney: origin of regenerating cells after renal ischemia

Maeshima, Akito

doi:10.1007/s10157-007-0500-9

Cited by 22 publications

(14 citation statements)

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“…Following damage, tubule cells partially dedifferentiate and become proliferative (Humphreys and Bonventre, 2007;Maeshima, 2007). Recent fate-mapping experiments strongly support the notion that tubule epithelial cells are responsible for the generation of new kidney cells (Duffield and Humphreys, 2011).…”

Section: Current Expression Of Byn-gal4 Is Visualized By Uas-gfp (Grementioning

confidence: 84%

Migration ofDrosophilaintestinal stem cells across organ boundaries

et al. 2013

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All components of the Drosophila intestinal tract, including the endodermal midgut and ectodermal hindgut/Malpighian tubules, maintain populations of dividing stem cells. In the midgut and hindgut, these stem cells originate from within larger populations of intestinal progenitors that proliferate during the larval stage and form the adult intestine during metamorphosis. The origin of stem cells found in the excretory Malpighian tubules (‘renal stem cells’) has not been established. In this paper, we investigate the migration patterns of intestinal progenitors that take place during metamorphosis. Our data demonstrate that a subset of adult midgut progenitors (AMPs) move posteriorly to form the adult ureters and, consecutively, the renal stem cells. Inhibiting cell migration by AMP-directed expression of a dominant-negative form of Rac1 protein results in the absence of stem cells in the Malpighian tubules. As the majority of the hindgut progenitor cells migrate posteriorly and differentiate into hindgut enterocytes, a group of the progenitor cells, unexpectedly, invades anteriorly into the midgut territory. Consequently, these progenitor cells differentiate into midgut enterocytes. The midgut determinant GATAe is required for the differentiation of midgut enterocytes derived from hindgut progenitors. Wingless signaling acts to balance the proportion of hindgut progenitors that differentiate as midgut versus hindgut enterocytes. Our findings indicate that a stable boundary between midgut and hindgut/Malpighian tubules is not established during early embryonic development; instead, pluripotent progenitor populations cross in between these organs in both directions, and are able to adopt the fate of the organ in which they come to reside.

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Section: Current Expression Of Byn-gal4 Is Visualized By Uas-gfp (Grementioning

confidence: 84%

Migration ofDrosophilaintestinal stem cells across organ boundaries

et al. 2013

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“…Mounting evidence from targeted inactivation of Nf2 in other tissues suggests that tissue progenitor cells are particularly sensitive to loss of Merlin (M. Curto, S. Benhamouche, A. Gladden, and A.I.M., unpublished data). In fact, Nf2 deficiency results in a dramatic increase in the number of label-retaining putative progenitor cells in the kidney, and polypoid tumors in the Nf2-deficient renal epithelium initiate at the corticomedullary junction, a region thought to harbor the progenitor cell niche in the adult kidney (35)(36)(37). It is tempting to speculate that a kidney progenitor cell is particularly sensitive to loss of Merlin-mediated, contact-dependent inhibition of proliferation in vivo and that this is the cell of origin of RCC in this model and perhaps in some cases of human RCC.…”

Section: Discussionmentioning

confidence: 99%

Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma

Morris

McClatchey

2009

Proc. Natl. Acad. Sci. U.S.A.

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The epidermal growth factor receptor (EGFR) has frequently been implicated in hyperproliferative diseases of renal tubule epithelia. We have shown that the NF2 tumor suppressor Merlin inhibits EGFR internalization and signaling in a cell contact-dependent manner. Interestingly, despite the paucity of recurring mutations in human renal cell carcinoma (RCC), homozygous mutation of the NF2 gene is found in Ϸ2% of RCC patient samples in the Sanger COSMIC database. To examine the roles of Merlin and EGFR in kidney tumorigenesis, we generated mice with a targeted deletion of Nf2 in the proximal convoluted epithelium using a Villin-Cre transgene. All of these mice developed intratubular neoplasia by 3 months, which progressed to invasive carcinoma by 6 -10 months. Kidneys from these mice demonstrated marked hyperproliferation and a concomitant increase in label-retaining putative progenitor cells. Early lumenfilling lesions in this model exhibited hyperactivation of EGFR signaling, altered solubility of adherens junctions components, and loss of epithelial polarity. Renal cortical epithelial cells derived from either early or late lesions were dependent on EGF for in vitro proliferation and were arrested by pharmacologic inhibition of EGFR or re-expression of Nf2. These cells formed malignant tumors upon s.c. injection into immunocompromised mice before in vitro passage. Treatment of Vil-Cre;Nf2 lox/lox mice with the EGFR inhibitor erlotinib halted the proliferation of tumor cells. These studies give added credence to the role of EGFR signaling and perhaps Nf2 deficiency in RCC and describe a rare and valuable mouse model for exploring the molecular basis of this disease.EGFR ͉ kidney ͉ Merlin ͉ Nf2 ͉ renal cell carcinoma

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“…In a rat unilateral ureteral obstruction (UUO) model, LRCs were localized to both tubules and the interstitium of the fibrotic kidney. LRCs proliferated and migrated into the interstitium through the destroyed tubular basement membrane (32), thus suggesting that LRCs undergo EMT during renal fibrosis (17).…”

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confidence: 99%

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

Mishima

Maeshima

Miya

et al. 2013

American Journal of Physiology-Renal Physiology

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type Ca 2ϩ channels are densely distributed in sympathetic nerves that innervate renal tubules. However, the role of N-type Ca 2ϩ channels in renal fibrosis remains unknown. To address this issue, we examined the difference between the effects of amlodipine (an L-type Ca 2ϩ channel blocker) and cilnidipine (a dual L/N-type Ca 2ϩ channel blocker) on fibrotic changes using a rat unilateral ureteral obstruction (UUO) model. The expression of both L-type and N-type Ca 2ϩ channels was significantly upregulated in UUO kidneys compared with that in contralateral kidneys. There were no significant differences in mean blood pressure among the rats tested. Both amlodipine and cilnidipine significantly attenuated fibrotic changes in UUO kidneys. The antifibrotic effect of cilnidipine was more potent than that of amlodipine. Amlodipine as well as cilnidipine reduced type III collagen deposition, ␣-smooth muscle actin (␣-SMA) expression, and interstitial cell proliferation. In addition, cilnidipine significantly reduced deposition of type I collagen and macrophage infiltration in UUO kidneys. With the use of in vivo bromodeoxyuridine labeling, label-retaining cells (LRCs) were identified as a population of tubular cells that participate in epithelial-mesenchymal transition after UUO. Some LRCs migrated into the interstitium, expressed ␣-SMA and vimentin, and produced several extracellular matrixes in UUO kidneys. The number of interstitial LRCs was significantly decreased by cilnidipine but not amlodipine. These data suggest that N-type Ca 2ϩ channels contribute to multiple steps of renal fibrosis, and its blockade may thus be a useful therapeutic approach for prevention of renal fibrosis.N-type calcium channel; renal fibrosis; unilateral ureteral obstruction; epithelial-mesenchymal transition THE RENAL SYMPATHETIC NERVES innervate the tubules, the vessels, and the juxtaglomerular granular cells of the kidney (5). Renal sympathetic nerve activation reduces urinary sodium and water excretion by increasing renal tubular water and sodium reabsorption throughout the nephron. It also decreases renal blood flow and glomerular filtration rate by constricting the renal vasculature and activates the renin-angiotensin system (RAS) by stimulating renin release from juxtaglomerular granular cells. Conversely, angiotensin II stimulates sympathetic nerve activity through central mechanisms and by facilitating adrenergic neurotransmission at the sympathetic nerve terminal, thus suggesting significant interactions between renal sympathetic nerves and the RAS in the control of renal function (4). N-type Ca 2ϩ channels are densely distributed in the sympathetic nervous system and play a predominant role in neurotransmitter release from the nerve endings of sympathetic neurons (8). In patients with chronic renal diseases, increased sympathetic nerve activity and plasma renin activity are observed (10), thus suggesting that sympathetic nerve activity via N-type Ca 2ϩ channels is involved in renal injury. Renal fibrosis is the common end point o...

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Label-retaining cells in the kidney: origin of regenerating cells after renal ischemia

Cited by 22 publications

References 46 publications

Migration ofDrosophilaintestinal stem cells across organ boundaries

Migration ofDrosophilaintestinal stem cells across organ boundaries

Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

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Label-retaining cells in the kidney: origin of regenerating cells after renal ischemia

Cited by 22 publications

References 46 publications

Migration ofDrosophilaintestinal stem cells across organ boundaries

Migration ofDrosophilaintestinal stem cells across organ boundaries

Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma

Involvement of N-type Ca2+channels in the fibrotic process of the kidney in rats

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Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats