Attenuated expression of epithelial cell adhesion molecules in murine polycystic kidney disease

Polycystic kidney disease is an inherited disorder of parenchymal structure that leads to renal failure. Cysts begin as focal dilations in proximal tubules and collecting ducts, giving rise to cyst walls lined by a phenotypically disturbed epithelium that expresses dysfunctional transport and matrix proteins. We used an mRNA search protocol to probe efficiently for tissue-specific disturbances that might underlie the formation of cysts. This search assessed the relative abundance of transcripts encoding a variety of growth factors (transforming growth factor-beta 1, interleukin-6, tumor necrosis factor, and endothelin-1), structural proteins (collagen IV, nidogen, fibronectin, and laminins A and B1), and cell adhesion molecules (CAMs; E-cadherin, N-CAM, laminin receptor, and fibronectin receptor) in the cystic kidneys of cpk/cpk mice and uncovered a previously unrecognized early reduction in mRNA encoding N-CAM (54%) and E-cadherin (56%) (n = 5; P less than 0.001). Levels of transcripts for growth factors, structural proteins, and for fibronectin and laminin receptors in normal and cystic kidneys were generally similar. The reduction in transcripts for N-CAM and E-cadherin in kidneys from cystic mice was not observed in autologous liver. The immunofluorescent staining of cystic kidneys confirmed that the decrease in N-CAM and E-cadherin was generally confined to regions abundant in developing cystic epithelium. The presence of both N-CAM and E-cadherin appears to guide the sequential differentiation and polarization of normal renal epithelium, and their attenuated expression in the kidney of cpk/cpk mice may be a material factor contributing to the pathogenesis of cyst formation.

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Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00038.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. F511-F520 ◽

Cited By ~ 30

Author(s):

Hiroko Togawa ◽

Koichi Nakanishi ◽

Hironobu Mukaiyama ◽

Taketsugu Hama ◽

Yuko Shima ◽

...

Keyword(s):

Kidney Disease ◽

Epithelial Cells ◽

Polycystic Kidney Disease ◽

Autosomal Recessive ◽

Epithelial To Mesenchymal Transition ◽

Cell Contact ◽

Polycystic Kidney ◽

Mesenchymal Transition ◽

Cyst Lining ◽

E Cadherin

In polycystic kidney disease (PKD), cyst lining cells show polarity abnormalities. Recent studies have demonstrated loss of cell contact in cyst cells, suggesting induction of epithelial-to-mesenchymal transition (EMT). Recently, EMT has been implicated in the pathogenesis of PKD. To explore further evidence of EMT in PKD, we examined age- and segment-specific expression of adhesion molecules and mesenchymal markers in PCK rats, an orthologous model of human autosomal-recessive PKD. Kidneys from 5 male PCK and 5 control rats each at 0 days, 1, 3, 10, and 14 wk, and 4 mo of age were serially sectioned and stained with segment-specific markers and antibodies against E-cadherin, Snail1, β-catenin, and N-cadherin. mRNAs for E-cadherin and Snail1 were quantified by real-time PCR. Vimentin, fibronectin, and α-smooth muscle actin (α-SMA) expressions were assessed as mesenchymal markers. E-cadherin expression pattern was correlated with the disease pathology in that tubule segments showing the highest expression in control had much severer cyst formation in PCK rats. In PCK rats, E-cadherin and β-catenin in cystic tubules was attenuated and localized to lateral areas of cell-cell contact, whereas nuclear expression of Snail1 increased in parallel with cyst enlargement. Some epithelial cells in large cysts derived from these segments, especially in adjacent fibrotic areas, showed positive immunoreactivity for vimentin and fibronectin. In conclusion, these findings suggest that epithelial cells in cysts acquire mesenchymal features in response to cyst enlargement and participate in progressive renal fibrosis. Our study clarified the nephron segment-specific cyst profile related to EMT in PCK rats. EMT may play a key role in polycystic kidney disease.

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Expression of CD44 and E-cadherin cell adhesion molecules in hypertrophied bladders during chronic partial urethral obstruction and after release of partial obstruction in rats

Urology ◽

10.1016/j.urology.2004.12.006 ◽

2005 ◽

Vol 65 (5) ◽

pp. 1013-1018 ◽

Cited By ~ 4

Author(s):

Hayrettin Ozturk ◽

Hulya Ozturk ◽

Ensari Guneli ◽

Yusuf Yagmur ◽

Huseyin Buyukbayram

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Urethral Obstruction ◽

Partial Obstruction ◽

E Cadherin

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Differences in E-Cadherin and Syndecan-1 Expression in Different Types of Ameloblastomas

Analytical Cellular Pathology ◽

10.1155/2018/9392632 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ramón G. Carreón-Burciaga ◽

Rogelio González-González ◽

Nelly Molina-Frechero ◽

Sandra López-Verdín ◽

Vanesa Pereira-Prado ◽

...

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Tumor Size ◽

Cell Adhesion Molecules ◽

Strong Association ◽

Tumor Aggressiveness ◽

Future Studies ◽

Unicystic Ameloblastoma ◽

Different Types ◽

E Cadherin

Ameloblastomas are a group of benign, locally aggressive, recurrent tumors characterized by their slow and infiltrative growth. E-Cadherin and syndecan-1 are cell adhesion molecules related to the behavior of various tumors, including ameloblastomas. Ninety-nine ameloblastoma samples were studied; the expression of E-cadherin and syndecan-1 were evaluated by immunohistochemistry. E-Cadherin and epithelial syndecan-1 were more highly expressed in intraluminal/luminal unicystic ameloblastoma than in mural unicystic ameloblastoma and solid/multicystic ameloblastoma, whereas the stromal expression of syndecan-1 was higher in mural unicystic ameloblastoma and solid/multicystic ameloblastoma. Synchronicity was observed between E-cadherin and epithelial syndecan-1; the expression was correlated with intensity in all cases. There was a strong association between expression and tumor size and recurrence. The evaluation of the expression of E-cadherin and syndecan-1 are important for determining the potential aggressiveness of ameloblastoma variants. Future studies are required to understand how the expression of these markers is related to tumor aggressiveness.

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Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro.

Journal of Histochemistry & Cytochemistry ◽

10.1177/42.10.7930515 ◽

1994 ◽

Vol 42 (10) ◽

pp. 1333-1340 ◽

Cited By ~ 25

Author(s):

Y Horiguchi ◽

F Furukawa ◽

M Fujita ◽

S Imamura

Keyword(s):

Cell Adhesion ◽

Free Surface ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Cytoplasmic Membrane ◽

Ultrastructural Localization ◽

In Vivo Studies ◽

E Cadherin

We examined the ultrastructural localization of E (epithelial)-cadherin cell adhesion molecules by immunoperoxidase electron microscopy on the epithelium of mouse intestine, epidermis of human skin, and cultured human keratinocytes. The in vivo studies demonstrated that E-cadherin was present at the intermediate junction but not at the desmosome of the mouse intestinal single epithelium, and was found on the cytoplasmic membranes of keratinocytes with condensation in the intercellular space of the desmosomes, except for the basal surface of the basal cells. In vitro studies demonstrated that keratinocytes cultured in medium containing a low Ca2+ concentration (0.1 mM) lacked the tight connection through desmosomes, and that E-cadherin showed diffuse distribution and dot-like accumulation around the free surface of the cytoplasmic membrane. In culture medium containing a high concentration of Ca2+ (0.6 mM), keratinocytes formed desmosomal adhesion structures in which E-cadherin was accumulated. The free surface of the keratinocytes in this medium showed weaker distribution and a lesser amount of dot-like accumulation of E-cadherin than that in a low Ca2+ condition. These findings suggest that the distribution pattern of the E-cadherin cell adhesion molecules on the keratinocytes is different from that on the single epithelium of the intestine, and that E-cadherin on the cytoplasmic membrane of the keratinocytes shifts to the desmosomes under physiological conditions, participating in adhesion in association with other desmosomal cadherins.

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Apoptosis in polycystic kidney disease: involvement of caspases

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.3.r763 ◽

2000 ◽

Vol 278 (3) ◽

pp. R763-R769 ◽

Cited By ~ 31

Author(s):

Shujath M. Ali ◽

Victoria Y. Wong ◽

Kristine Kikly ◽

Todd A. Fredrickson ◽

Paul M. Keller ◽

...

Keyword(s):

Cell Death ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Apoptotic Cell ◽

Renal Cysts ◽

Terminal Deoxynucleotidyl Transferase ◽

Homozygous Mutation ◽

Polycystic Kidney ◽

Apoptosis Pathway ◽

Cystic Kidneys

Polycystic kidney disease (PKD) is characterized by the development of large renal cysts and progressive loss of renal function. Although the cause of the development of renal cysts is unknown, recent evidence suggests that excessive apoptosis occurs in PKD. With the use of terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, we have confirmed the presence of apoptotic bodies in cystic kidneys of congenital polycystic kidney (cpk) disease mice carrying a homozygous mutation at 3 wk of age. Apoptosis was localized primarily to the interstitium with little evidence of cell death in cyst epithelium or noncystic tubules. In addition, we observed that the expression of various caspases, bax and bcl-2, was upregulated in cystic kidneys. With the use of various substrates in enzyme activity assays, we have demonstrated a greater than sevenfold increase in caspase 4 activity and a sixfold increase in caspase 3 activity. These data suggest that there is a caspase-dependent apoptosis pathway associated with PKD and support the hypothesis that apoptotic cell death contributes to cyst formation in PKD.

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Pkd1-targeted mutation reveals a role for the Wolffian duct in autosomal dominant polycystic kidney disease

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174419000436 ◽

2019 ◽

Vol 11 (1) ◽

pp. 78-85 ◽

Cited By ~ 1

Author(s):

J. B. Tee ◽

A. V. Dnyanmote ◽

M. K. Lorenzo ◽

O. R. Lee ◽

S. Grisaru ◽

...

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

High Throughput Sequencing ◽

Autosomal Dominant ◽

Cyst Formation ◽

Wolffian Duct ◽

Renal Tubules ◽

Polycystic Kidney ◽

Cystic Kidneys ◽

Autosomal Dominant Polycystic Kidney

AbstractSeveral life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.

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The child with renal cysts

10.1093/med/9780199592548.003.0305 ◽

2015 ◽

Author(s):

Carsten Bergmann ◽

Nadina Ortiz-Brüchle ◽

Valeska Frank ◽

Klaus Zerres

Keyword(s):

Family History ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Renal Cysts ◽

Polycystic Kidney ◽

Polycystic Kidneys ◽

Cystic Kidneys ◽

Common Diagnosis ◽

The Family ◽

Autosomal Dominant Polycystic Kidney

Renal cysts of different aetiology are a common diagnosis in paediatric nephrology. The classification is usually based on the clinical picture, morphology, and family history. In syndromic forms, additional features have to be evaluated. Most common are cystic dysplastic kidneys with a broad phenotypic spectrum ranging from asymptomatic clinical courses in unilateral cases to severe, lethal manifestations in patients with considerable bilateral involvement. Simple cysts are rare. Polycystic kidneys are usually subdivided according to the mode of inheritance into autosomal recessive and autosomal dominant polycystic kidney disease. The most useful investigation in order to distinguish between these two types is the family history with parental ultrasound and demonstration of polycystic kidneys in one parent in the majority of cases with dominant polycystic kidney disease. Finally, cystic kidneys are associated with a variety of hereditary, usually recessive syndromes affecting cilia.

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Inversin Forms a Complex with Catenins and N-Cadherin in Polarized Epithelial Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e02-04-0195 ◽

2002 ◽

Vol 13 (9) ◽

pp. 3096-3106 ◽

Cited By ~ 74

Author(s):

Jens Nürnberger ◽

Robert L. Bacallao ◽

Carrie L. Phillips

Keyword(s):

Cell Adhesion ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Polyclonal Antibodies ◽

Cell Monolayer ◽

Renal Cysts ◽

Cell Junctions ◽

Metanephric Mesenchyme ◽

Polycystic Kidney ◽

Cell Cell

Nephrogenesis starts with the reciprocal induction of two embryonically distinct analages, metanephric mesenchyme and ureteric bud. This complex process requires the refined and coordinated expression of numerous developmental genes, such as inv. Mice that are homozygous for a mutation in the inv gene (inv/inv) develop renal cysts resembling autosomal-recessive polycystic kidney disease. The gene locus containing inv has been proposed to serve as a common modifier for some human and rodent polycystic kidney disease phenotypes. We generated polyclonal antibodies to inversin to study its subcellular distribution, potential binding partners, and functional aspects in cultured murine proximal tubule cells. A 125-kDa inversin protein isoform was found at cell-cell junctions. Two inversin isoforms, 140- and 90-kDa, were identified in the nuclear and perinuclear compartments. Plasma membrane allocation of inversin is dependent upon cell-cell contacts and was redistributed when cell adhesion was disrupted after incubation of the cell monolayer with low-calcium/EGTA medium. We further show that the membrane-associated 125-kDa inversin forms a complex with N-cadherin and the catenins. The 90-kDa nuclear inversin complexes with β-catenin. These findings indicate that the inv gene product functions in several cellular compartments, including the nucleus and cell-cell adhesion sites.

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