scholarly journals Epithelial Cell TGFβ Signaling Induces Acute Tubular Injury and Interstitial Inflammation

2013 ◽  
Vol 24 (5) ◽  
pp. 787-799 ◽  
Author(s):  
Madeleine E. Gentle ◽  
Shaolin Shi ◽  
Ilse Daehn ◽  
Taoran Zhang ◽  
Haiying Qi ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Tubular Injury ◽  
Tgfβ Signaling ◽  
Interstitial Inflammation

scholarly journals Tubular Injury and Dendritic Cell Activation Are Integral Components of Light Chain–Associated Acute Tubulointerstitial Nephritis

2019 ◽  
Vol 143 (10) ◽  
pp. 1212-1224 ◽  
Author(s):  
Mingyu Cheng ◽  
Xin Gu ◽  
Elba A. Turbat-Herrera ◽  
Guillermo A. Herrera
Keyword(s):  
Dendritic Cells ◽  
Light Chain ◽  
Tubulointerstitial Nephritis ◽  
Light Chains ◽  
Tubular Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Interstitial Inflammation ◽  
Biopsy Specimens ◽  
Proximal Tubular

Context.— Light chain–associated acute tubulointerstitial nephritis (LC-ATIN) is a variant of light chain proximal tubulopathy (LCPT). It is characterized by interstitial inflammation with tubulitis and deposition of monoclonal light chains in the tubulointerstitium. LC-ATIN is a rather poorly recognized pattern of LCPT and not much is known about this entity. Objective.— To determine the clinicopathologic features of patients with LC-ATIN and investigate the proximal tubular injury and mechanism of interstitial inflammation in LC-ATIN. Design.— A total of 38 cases of LC-ATIN were identified from the archives of 5043 renal biopsy specimens. In all cases, routine light microscopic examination, immunofluorescence, and electron microscopic examination were performed. In selected cases, immunofluorescent staining of dendritic cells and immunohistochemical staining for 4 tubular injury markers—KIM-1, p53, bcl-2, and Ki-67—were performed. Results.— A characteristic finding in LC-ATIN cases was immunofluorescence staining of monoclonal light chains along tubular basement membranes in linear fashion and inside proximal tubular cells with a granular pattern. No monoclonal light chains were present in glomerular or vascular compartments confirmed with immunofluorescence, electron microscopy, and ultrastructural gold labeling. Ten of 15 LC-ATIN cases (67%) were concurrently positive for the 4 tubular injury markers. Dendritic cells were identified within the tubulointerstitium in the renal biopsy specimens, interacting with surrounding tubules with light-chain deposits and inflammatory cells. Conclusions.— Significant proximal tubular injury occurs associated with LC-ATIN, and the monoclonal light chains accumulated in proximal tubular cells contribute to the injury. Dendritic cells are involved in the pathogenesis of interstitial inflammation in LC-ATIN.

scholarly journals Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia

2011 ◽  
Vol 301 (6) ◽  
pp. F1346-F1357 ◽  
Author(s):  
Patricia W. Seo-Mayer ◽  
Gunilla Thulin ◽  
Li Zhang ◽  
Daiane S. Alves ◽  
Thomas Ardito ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Plasma Membrane ◽  
Epithelial Cell ◽  
Mdck Cells ◽  
Cell Damage ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
In Vivo Studies ◽  
Tubular Injury ◽  
Energy Depletion

Alterations in epithelial cell polarity and in the subcellular distributions of epithelial ion transport proteins are key molecular consequences of acute kidney injury and intracellular energy depletion. AMP-activated protein kinase (AMPK), a cellular energy sensor, is rapidly activated in response to renal ischemia, and we demonstrate that its activity is upregulated by energy depletion in Madin-Darby canine kidney (MDCK) cells. We hypothesized that AMPK activity may influence the maintenance or recovery of epithelial cell organization in mammalian renal epithelial cells subjected to energy depletion. MDCK cells were ATP depleted through a 1-h incubation with antimycin A and 2-deoxyglucose. Immunofluoresence localization demonstrated that this regimen induces mislocalization of the Na-K-ATPase from its normal residence at the basolateral plasma membrane to intracellular vesicular compartments. When cells were pretreated with the AMPK activator metformin before energy depletion, basolateral localization of Na-K-ATPase was preserved. In MDCK cells in which AMPK expression was stably knocked down with short hairpin RNA, preactivation of AMPK with metformin did not prevent Na-K-ATPase redistribution in response to energy depletion. In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury. Thus AMPK may play a role in preserving the functional integrity of epithelial plasma membrane domains in the face of energy depletion. Furthermore, pretreatment with an AMPK activator before ischemia may attenuate the severity of renal tubular injury in the context of acute kidney injury.

scholarly journals Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis

2016 ◽  
Vol 311 (1) ◽  
pp. F35-F45 ◽  
Author(s):  
Hayley Beaton ◽  
Darrell Andrews ◽  
Martin Parsons ◽  
Mary Murphy ◽  
Andrew Gaffney ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cell ◽  
Animal Models ◽  
Epithelial Cells ◽  
Renal Fibrosis ◽  
Critical Role ◽  
Functional Characterization ◽  
Nuclear Accumulation ◽  
Tubular Injury ◽  
Renal Epithelial Cells

Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis, and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and frizzled 7 (FzD7) expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, TCF/Lef reporter activity is also prominent in the mesonephros. Analysis of Wnt family members in human renal biopsies identified differential expression of Wnt6, correlating with severity of the disease. In animal models of tubular injury and fibrosis, loss of Wnt6 was evident. Wnt6 signals through the canonical pathway in renal epithelial cells as evidenced by increased phosphorylation of GSK3β (Ser9), nuclear accumulation of β-catenin and increased TCF/Lef transcriptional activity. FzD7 was identified as a putative receptor of Wnt6. In vitro Wnt6 expression leads to de novo tubulogenesis in renal epithelial cells grown in three-dimensional culture. Importantly, Wnt6 rescued epithelial cell dedifferentiation in response to transforming growth factor-β (TGF-β); Wnt6 reversed TGF-β-mediated increases in vimentin and loss of epithelial phenotype. Wnt6 inhibited TGF-β-mediated p65-NF-κB nuclear translocation, highlighting cross talk between the two pathways. The critical role of NF-κB in the regulation of vimentin expression was confirmed in both p65−/−and IKKα/β−/−embryonic fibroblasts. We propose that Wnt6 is involved in epithelialization and loss of Wnt6 expression contributes to the pathogenesis of renal fibrosis.

scholarly journals Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

2018 ◽  
Vol 6 (6) ◽  
pp. e13654 ◽  
Author(s):  
Olena Maydan ◽  
Paul G. McDade ◽  
Yan Liu ◽  
Xue-Ru Wu ◽  
Douglas G. Matsell ◽  
...  
Keyword(s):  
Obstructive Nephropathy ◽  
Tubular Injury ◽  
Interstitial Inflammation

scholarly journals Diagnostic roles of urinary kidney injury molecule 1 and soluble C5b-9 in acute tubulointerstitial nephritis

2019 ◽  
Vol 317 (3) ◽  
pp. F584-F592 ◽  
Author(s):  
Wen-Ting Zhao ◽  
Jun-Wen Huang ◽  
Ping-Ping Sun ◽  
Tao Su ◽  
Jia-Wei Tang ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Kidney Injury ◽  
Acute Injury ◽  
Tubular Injury ◽  
Acute Tubulointerstitial Nephritis ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Interstitial Inflammation ◽  
Renal Tubular ◽  
Kidney Injury Molecule 1

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury characterized by inflammatory cells infiltrating in the interstitium. The present study aimed to explore noninvasive biomarkers that might indicate activity of pathological injuries and help direct treatment. Fifty-four patients with clinical-pathologically diagnosed ATIN from January 1, 2014, to June 30, 2016, at Peking University First Hospital were enrolled. Urine samples were collected on the morning of renal biopsy and assessed for urinary kidney injury molecule-1 (KIM-1) and urinary soluble C5b-9 (sC5b-9). Immunofluorescence staining for KIM-1 and C5b-9 was performed in biopsied kidney sections from ATIN cases. The clinical and pathological relevance of the two urinary biomarkers was analyzed. Both urinary KIM-1 and sC5b-9 values were significantly elevated in patients with ATIN compared with healthy controls. The urinary KIM-1 level positively correlated with urinary N-acetyl-β-d-glucosaminidase ( r = 0. 542, P = 0.001) and the pathological tubular injury score ( r = 0.469, P < 0.001), whereas the urinary sC5b-9 level was related to pathological activity scores for tubular injury ( r = 0.413, P = 0.002), interstitial inflammation ( r = 0.388, P = 0.004), and treatment response ( r = 0.564, P < 0.001). Urinary KIM-1 tended to have better diagnostic value for tubular injury than urinary sC5b-9, whereas only urinary sC5b-9 was able to demonstrate severe interstitial inflammation. A combination of urinary KIM-1 and sC5b-9 had an area under the receiver-operating characteristic curve of 0.864 (95% confidence interval: 0.766–0.963, P < 0.001, sensitivity: 75%, specificity: 88%) for acute tissue injury in ATIN. KIM-1 expression was markedly increased in renal tubular cells in both ATIN and acute tubular necrosis conditions, whereas a significant upregulation of C5b-9 was only detected in the tubular cells and interstitial cells in ATIN cases. Urinary KIM-1 is a specific biomarker for renal tubular injury in ATIN, whereas urinary sC5b-9 is valuable in demonstrating severe interstitial inflammation. The combination of these two biomarkers helps identify patients at an acute injury stage and, therefore, might facilitate clinical evaluation and guide immunosuppressive therapy.

1135: Apatite Deposits in Collecting Duct Lumens Produce Epithelial Cell Injury and Interstitial Inflammation in Patients Forming Brushite Renal Stones

2004 ◽  
Vol 171 (4S) ◽  
pp. 299-299 ◽  
Author(s):  
Andrew P. Evan ◽  
James E. Lingeman ◽  
Fredric L. Coe ◽  
Youzhi Shao ◽  
Joan H. Parks ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Injury ◽  
Collecting Duct ◽  
Renal Stones ◽  
Interstitial Inflammation ◽  
Epithelial Cell Injury

Electron Microscopic Study of the Epithelium of the Seminal Vesicle of Aging Rats

1974 ◽  
Vol 32 ◽  
pp. 138-139
Author(s):  
V. F. Allison ◽  
G. C. Fink ◽  
G. W. Cearley
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Seminal Vesicle ◽  
Seminal Vesicles ◽  
Epithelial Layer ◽  
Epithelial Hyperplasia ◽  
Electron Microscopic ◽  
Aging Rats ◽  
Pseudostratified Epithelium

It is well known that epithelial hyperplasia (benign hypertrophy) is common in the aging prostate of dogs and man. In contrast, little evidence is available for abnormal epithelial cell growth in seminal vesicles of aging animals. Recently, enlarged seminal vesicles were reported in senescent mice, however, that enlargement resulted from increased storage of secretion in the lumen and occurred concomitant to epithelial hypoplasia in that species.The present study is concerned with electron microscopic observations of changes occurring in the pseudostratified epithelium of the seminal vescles of aging rats. Special attention is given to certain non-epithelial cells which have entered the epithelial layer.

Intranuclear Crystals in Regenerating Canine Kidneys

1973 ◽  
Vol 31 ◽  
pp. 412-413
Author(s):  
D.G. Osborne ◽  
L.J. McCormack ◽  
M.O. Magnusson ◽  
W.S. Kiser
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tubular Epithelial Cell ◽  
Tubular Epithelial Cells ◽  
Cell Nuclei ◽  
Crystalline Structures ◽  
Small Crystals ◽  
Membrane Bound

During a project in which regenerative changes were studied in autotransplanted canine kidneys, intranuclear crystals were seen in a small number of tubular epithelial cells. These crystalline structures were seen in the control specimens and also in regenerating specimens; the main differences being in size and number of them. The control specimens showed a few tubular epithelial cell nuclei almost completely occupied by large crystals that were not membrane bound. Subsequent follow-up biopsies of the same kidneys contained similar intranuclear crystals but of a much smaller size. Some of these nuclei contained several small crystals. The small crystals occurred at one week following transplantation and were seen even four weeks following transplantation. As time passed, the small crystals appeared to fuse to form larger crystals.

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