Ischemia-induced loss of epithelial polarity. Role of the tight junction.

Molitoris, Bruce A.; Falk, Sandor; Dahl, Rolf

doi:10.1172/jci114302

Cited by 134 publications

(59 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment with antimycin A is an established method to cause a reversible depletion of ATP and opening of tight junctions in epithelial cells. 32 We observed 24% cell death after 30 min of antimycin A incubation. Three days after addition of BMC, occasional cells with 3X1Y chromosomes were detected, indicating fusion of BMC with renal epithelial cells ( Figure 7A-c).…”

Section: Fusion Of Bmc With Tubular Epithelial Cells After Cellular Imentioning

confidence: 71%

Renal and Bone Marrow Cells Fuse after Renal Ischemic Injury

Li¹,

Truong²,

Igarashi³

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

After acute kidney injury, bone marrow cells contribute to renal repair by converting into renal cells, but the mechanism of this conversion is not well understood. To determine whether cell fusion between bone marrow cells and injured renal cells plays a role, we subjected female mice expressing Cre recombinase in tubular epithelial cells to unilateral renal ischemia-reperfusion injury, and subsequently transplanted male bone marrow cells containing a loxP-flanked reporter gene. After 28 days, cell fusion was detected by polysomy for the sex chromosomes and Cre-mediated activation of the reporter gene. After injury, 1.8% of tubular cells were bone marrow-derived, but Cre/loxP recombination demonstrated a frequency of fusion between tubular epithelial and bone marrow cells of only 0.066% (approximately 7 per 10,000 tubular cells). The second strategy, chromosome fluorescence in situ hybridization (FISH), detected cell fusion in 3.8% of bone marrow-derived tubular epithelial cells. No cell fusion was observed in nonischemic kidneys, suggesting that injury was required for cell fusion. This finding was substantiated in co-culture experiments, because cell fusion was only observed between bone marrow cells and renal tubular cells when the latter were depleted of ATP. In conclusion, bone marrow cells can fuse with renal epithelial cells after ischemic injury, but the low frequency of fusion does not account for the majority of the observed conversion of bone marrow cells into kidney cells.

show abstract

Section: Fusion Of Bmc With Tubular Epithelial Cells After Cellular Imentioning

confidence: 71%

Renal and Bone Marrow Cells Fuse after Renal Ischemic Injury

Li¹,

Truong²,

Igarashi³

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…A potential explanation could be loss of epithelial cell-polarization and tight junction integrity in AKI, as has been shown in experimental studies and after human renal transplantation [35], making tubular sodium reabsorption less effi cient [36]. Another explana tion may be diminished renal nitric oxide (NO) genera tion because of endothelial damage and downregulation of endothelial NO synthase (eNOS/NOS-3).…”

Section: Renal Oxygenation In Clinical Ischemic Acute Kidney Injurymentioning

confidence: 99%

Renal Oxygenation in Clinical Acute Kidney Injury

Ricksten¹,

Bragadottir²,

Redfors³

2013

Annual Update in Intensive Care and Emergency Medicine 2013

View full text Add to dashboard Cite

Renal oxygenation is defi ned as the relationship between renal oxygen delivery (DO 2 ) and renal oxygen consumption (VO 2 ) and it can easily be shown that the inverse of this relationship is equivalent to renal extraction of O 2 (O 2 Ex). An increase in renal O 2 Ex means that renal DO 2 has decreased in relation to renal VO 2 , i. e., renal oxygenation is impaired, and vice versa. When compared to other major organs, renal VO 2 is relatively high, second only to the heart. In sedated, mechanically ventilated patients, renal VO 2 is two-thirds (10 ml/min) that of myocardial oxygen consumption (15 ml/min) (Table 1) [1,2]. Renal blo od fl ow, w hich accounts for approximately 20 % of cardiac output, is three times higher than myocardial blood fl ow in this group of patients. Renal O 2 Ex in the non-failing kidney is therefore low, 10 %, compared with, e.g., the heart, in which O 2 E X is 55 % (Table 1). Determin a nts of renal oxygenationIt is well known from experimental studies that tubular sodium reabsorption is the major determinant of renal VO 2 [3] and tha t under normal physiological conditions, approximately 80 % is used to drive active tubular transport of particularly sodium, but also glucose, amino acids and other solutes. Tubular transport processes are highly load-dependent and it has been shown in experimental studies [4] and in p atients [2,[5][6][7] that the re i s a close linear correlation between glomerular fi ltration rate (GFR), renal sodium reabsorption and renal VO 2 (Fig. 1). Th e fi l tered load of sodium is, thus, an important determi nant of renal VO 2 and maneuvers that decrease GFR and the tubular sodium load act to decrease tubular sodium reabsorption and renal VO 2 , and vice versa [8]. It has b een shown that renal O 2 Ex remains stable over a wide range of renal blood fl ows, which means that changes in renal DO 2 , caused by changes in renal blood fl ow, are directly off set by changes in renal VO 2 [9], i. e., r enal VO 2 is fl ow-dependent. Th us, unlike other organs where increases in blood fl ow will improve oxygenation, increased renal blood fl ow augments GFR and the fi ltered load of sodium, which will increase renal VO 2 . Due to this fl ow-dependency of renal VO 2 , renal oxygenation will re main constant, as long as renal blood fl ow and GFR change in parallel. Regional intrarenal oxygenation and medullary hypoxiaTh e relatively high renal blood fl ow is directed preferentially to the cortex to optimize the fi ltration process and solute reabsorption. In contrast, blood fl ow in the outer medulla is less than 50 % of the cortical blood fl ow to preserve osmotic gradients and to enhance urinary concentration [10]. Th e combi nation of low me dullary perfusion, high oxygen consumption of the medullary thick ascending limbs (mTAL) and the countercurrent exchange of oxygen within the vasa recta, results in a poorly oxygenated outer medulla [11]. Oxygen av ailability is, therefore, low in the outer medulla, which has an oxygen tissue partial pressure (PO 2 ) of 10-20 mm Hg ...

show abstract

“…However, ischemia in renal proximal tubule cells results in the rapid duration-dependent opening of tight junctions, which precedes or occurs concurrently with the redistribution of surface membrane phospholipids and Na',K+-ATPase to the alternate surface membrane domain (70). Microfilament disruption may also be involved in ischemic cell injury, as disruption of terminal web and microvillar actin microfilaments occurs early and in a time-dependent fashion (65).…”

Section: Altered Epithelial Cell Polarity In Pathologic Statesmentioning

confidence: 99%