Hepatocyte Growth Factor Alters the Polarity of Madin-Darby Canine Kidney Cell Monolayers

Balkovetz, Daniel F.; Pollack, Anne L.; Mostov, Keith E.

doi:10.1074/jbc.272.6.3471

Cited by 70 publications

(84 citation statements)

References 32 publications

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“…3C). On soft substrates, E-cadherin and ZO-1 were strongly localized to the basolateral and apical regions of cell-cell junctions, respectively, indicative of mature cell-cell contacts (Balkovetz et al, 1997). This localization to cell-cell contacts was most evident in interior cells, where the intensity of E-cadherin and ZO-1 staining at cell-cell interfaces exceeded the levels of these proteins within the cell body (see quantification in Fig.…”

Section: Substratum Compliance Affects the Maturation Of Cell-cell Comentioning

confidence: 92%

Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation

Kim

Asthagiri

2011

Journal of Cell Science

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Contact inhibition of proliferation is a hallmark of normal epithelial cells. By contrast, cancer cells over-ride this key constraint and proliferate in a contact-independent manner, leading to tumor formation (Hanahan and Weinberg, 2000). Contact inhibition is enforced in a rich microenvironment that includes conflicting mitogenic stimuli, such as soluble growth factors. Antagonistic interactions between growth factors and cell-cell contact are mediated through several mechanisms involving the atypical cadherin, Fat (protocadherin Fat 1), the ERM family proteins, Merlin and Expanded, the Hippo-YAP pathway and interactions between cadherins and growth factor receptors (Curto et al., 2007;Hamaratoglu et al., 2006;Lampugnani et al., 2003;Lampugnani et al., 2006;Yin and Pan, 2007).We recently demonstrated that this crosstalk has quantitative implications for contact inhibition in a microenvironment that includes the mitogen EGF (epidermal growth factor) (Kim et al., 2009). Cell-cell contact does not act as an autonomous switch and is titrated against the level of EGF to determine the net effect on cell proliferation. Only when the level of EGF is below a threshold amount does cell-cell contact inhibit proliferation, leading to a spatial pattern in proliferation in epithelial cell clusters. Furthermore, this threshold is a tuneable property. Enhancing cell-cell interactions either specifically by overexpressing E-cadherin or non-specifically by crowding cells in a micropatterned region elevates the EGF threshold. These quantitative features of contact inhibition are captured in a state diagram model (supplementary material Fig. S1).The state diagram model provides a quantitative framework for the contact dependence of cell proliferation. Cell cycle progression, however, is regulated by cell adhesion not only to its neighbors, but also to the ECM. In non-transformed cells, adhesion to the ECM is required for a full mitogenic response to growth factor stimulation (Lee and Juliano, 2004). The loss of ECM-dependent proliferation leads to anchorage-independent proliferation, another hallmark of cancer cells (Assoian, 1997). However, how anchoragedependent and contact-dependent proliferation are inter-related remains to be elucidated. This issue is particularly relevant in many physiological contexts in which epithelial cells are exposed to soluble growth factors while adhered to both an underlying ECM and to neighboring cells. How does the three-way crosstalk among cell-cell contact, ECM and growth factors quantitatively affect cell cycle regulation? How does the ECM factor into or modify the state diagram model?To begin to examine these questions, we focused on a physiologically significant property of the ECM: its mechanical compliance. Changes in ECM stiffness are associated with disease progression. A prominent example is the stiffening of the ECM during cancer progression and its role in metastasis and disruption of tissue architecture (Butcher et al., 2009;Levental et al., 2009). Matrix stiffness is now broadly app...

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Section: Substratum Compliance Affects the Maturation Of Cell-cell Comentioning

confidence: 92%

Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation

Kim

Asthagiri

2011

Journal of Cell Science

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“…33528 (Sigma, St. Louis, MO) diluted 1:1000 in PBS, and coverslips attached. Immunofluorescent labeling of polarized Madin-Darby canine kidney (MDCK) cells grown on filters was performed as previously described (Balkovetz et al, 1997). Identical results were obtained with all three sera.…”

Section: Immunolocalizationmentioning

confidence: 99%

Polaris, a Protein Involved in Left-Right Axis Patterning, Localizes to Basal Bodies and Cilia

Taulman

Haycraft

Balkovetz

et al. 2001

MBoC

Self Cite

294

257

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Mutations in Tg737 cause a wide spectrum of phenotypes, including random left-right axis specification, polycystic kidney disease, liver and pancreatic defects, hydrocephalus, and skeletal patterning abnormalities. To further assess the biological function of Tg737 and its role in the mutant pathology, we identified the cell population expressing Tg737 and determined the subcellular localization of its protein product called Polaris. Tg737 expression is associated with cells possessing either motile or immotile cilia and sperm. Similarly, Polaris concentrated just below the apical membrane in the region of the basal bodies and within the cilia or flagellar axoneme. The data suggest that Polaris functions in a ciliogenic pathway or in cilia maintenance, a role supported by the loss of cilia on the ependymal cell layer in ventricles of Tg737 orpk brains and by the lack of node cilia in Tg737 ⌬2-3␤Gal mutants.

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“…Proximal tubular cells were plated on Transwell filters (Corning) with a pore size of 0.4 μm. Polarization was confirmed with immunocytochemistry for ZO-1 as previously described (60). Rat mAb R40.76 against ZO-1 was a gift from D.F.…”

Section: Real-time Pcrmentioning

confidence: 99%

Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

Zarjou¹,

Bolisetty²,

Joseph³

et al. 2013

J. Clin. Invest.

178

166

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Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule-specific FtH-knockout mice (FtH PT-/-mice). FtH PT-/-mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtH PT-/-mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase-associated lipocalin, hemopexin, and transferrin were increased in FtH PT-/-mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI.

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Hepatocyte Growth Factor Alters the Polarity of Madin-Darby Canine Kidney Cell Monolayers

Cited by 70 publications

References 32 publications

Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation

Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation

Polaris, a Protein Involved in Left-Right Axis Patterning, Localizes to Basal Bodies and Cilia

Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

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