Induction of FGF-7 after kidney damage: a possible paracrine mechanism for tubule repair

1996 ◽  
Vol 271 (5) ◽  
pp. F967-F976 ◽  
Author(s):  
T. Ichimura ◽  
P. W. Finch ◽  
G. Zhang ◽  
M. Kan ◽  
J. L. Stevens
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Proximal Tubule ◽  
Collecting Duct ◽  
Keratinocyte Growth Factor ◽  
Interstitial Cells ◽  
Tubular Damage

A member of the fibroblast growth factor (FGF) family, keratinocyte growth factor (FGF-7 has unique specificity for epithelial cells. We investigated the role of FGF-7 in repair of proximal tubular damage caused by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). In situ hybridization localized FGF-7 to interstitial cells in the medulla and outer stripe of the outer medulla. Interstitial FGF-7 expression increased throughout the kidney 1 day after TFEC treatment. FGFR2 IIIb mRNA was high in the papilla and medulla and also increased after TFEC administration. By in situ hybridization, FGFR2 IIIb was localized to the tubular epithelium, particularly in collecting ducts. Proliferation of collecting duct epithelial cells increased in adult kidney after damage to the proximal tubule. FGFR2 IIIb, but not FGF-7, mRNA was also expressed by rat proximal tubule epithelial (RPTE) cells in vitro, and FGF-7 increased DNA synthesis in RPTE. Thus FGFR2 IIIb and FGF-7 expression is segregated between epithelial and interstitial cells forming a paracrine growth factor loop. These results raise the possibility that a novel paracrine growth loop is activated by chemical damage and regulates epithelial cell growth during tubular repair.

scholarly journals Localization of phosphatidylinositol phosphate kinase IIγ in kidney to a membrane trafficking compartment within specialized cells of the nephron

2008 ◽  
Vol 295 (5) ◽  
pp. F1422-F1430 ◽  
Author(s):  
Jonathan H. Clarke ◽  
Piers C. Emson ◽  
Robin F. Irvine
Keyword(s):  
Epithelial Cells ◽  
Membrane Trafficking ◽  
Kidney Cell ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Phosphatidylinositol Phosphate ◽  
The Matrix ◽  
Phosphatidylinositol 4

PIP4Ks (type II phosphatidylinositol 4-phosphate kinases) are phosphatidylinositol 5-phosphate (PtdIns5P) 4-kinases, believed primarily to regulate cellular PtdIns5P levels. In this study, we investigated the expression, localization, and associated biological activity of the least-studied PIP4K isoform, PIP4Kγ. Quantitative RT-PCR and in situ hybridization revealed that compared with PIP4Kα and PIP4Kβ, PIP4Kγ is expressed at exceptionally high levels in the kidney, especially the cortex and outer medulla. A specific antibody was raised to PIP4Kγ, and immunohistochemistry with this and with antibodies to specific kidney cell markers showed a restricted expression, primarily distributed in epithelial cells in the thick ascending limb and in the intercalated cells of the collecting duct. In these cells, PIP4Kγ had a vesicular appearance, and transfection of kidney cell lines revealed a partial Golgi localization (primarily the matrix of the cis-Golgi) with an additional presence in an unidentified vesicular compartment. In contrast to PIP4Kα, bacterially expressed recombinant PIP4Kγ was completely inactive but did have the ability to associate with active PIP4Kα in vitro. Overall our data suggest that PIP4Kγ may have a function in the regulation of vesicular transport in specialized kidney epithelial cells.

Human Immunodeficiency Virus Infection of Early Passage Cervical Epithelial Cultures

1993 ◽  
Vol 4 (6) ◽  
pp. 342-345 ◽  
Author(s):  
S L Patrick ◽  
T C Wright ◽  
H E Fox ◽  
H S Ginsberg
Keyword(s):  
In Situ Hybridization ◽  
Epithelial Cells ◽  
Female Genital Tract ◽  
Virus Production ◽  
Heterosexual Transmission ◽  
Early Passage ◽  
Epithelial Cultures ◽  
Cervical Epithelial Cells

Women are infected with HIV in increasing numbers; the predominant mode of spread is through heterosexual transmission. Little is known regarding the mechanism of HIV transit through the female genital tract. We investigated whether early passaage cervical epithelial cells could be directly infected with HIV-1LAI*. Virus production was measured using the reverse transcriptase (RT) assay and direct assay for syncytia-forming units. In-situ hybridization was performed on infected cervical cell cultures. Immunostaining was carried out using a monoclonal antibody to leukocyte common antigen (LCA). Virus was recovered in the supernatants of all infected cervical cultures. Localization of HIV infection using in-situ hybridization identified rare cells in the population which gave a strong signal. These infected cells had a lymphoid morphology and were also detected using immunostaining for LAC. Cervical epithelial cells were uninfected in this in vitro model; cells in this population which supported viral replication were most likely of the macrophage/monocyte lineage.

scholarly journals Distribution of vascular endothelial growth factor (VEGF) and its binding sites at the maternal-fetal interface during gestation in pigs

Reproduction ◽  
2001 ◽  
pp. 753-760 ◽  
Author(s):  
DS Charnock-Jones ◽  
DE Clark ◽  
D Licence ◽  
K Day ◽  
FB Wooding ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Ligand Binding ◽  
Vascular Endothelial ◽  
Epithelial Layers ◽  
Endothelial Growth Factor ◽  
Maternal Fetal Interface

Pigs show epitheliochorial placentation, in which the maternal uterine epithelium and the fetal trophectoderm become closely apposed. There is no invasion of trophoblast into the maternal tissue, and nutrient and waste exchange take place across two epithelial layers beneath which a complex network of capillaries forms. Later in gestation, the epithelial cells become indented by blood vessels, which greatly reduces the distance for diffusion between the two circulatory systems. Vascular endothelial growth factor is a secreted homodimeric angiogenic growth factor that is involved in physiological and pathological angiogenesis. Its receptors are generally restricted to endothelial cells. Ligand binding, in situ hybridization and immunohistochemistry were carried out in pig placenta throughout gestation to investigate the possible role of vascular endothelial growth factor and its receptors in non-invasive placentation. In situ hybridization and immunohistochemistry revealed that mRNA and immunoreactivity for vascular endothelial growth factor were localized in both maternal and fetal epithelial cells at the maternal-fetal interface and over the maternal glands, although the signal was generally weaker in the maternal glands. Ligand binding was used to localize for vascular endothelial growth factor receptors; no binding was observed over the maternal glands, but very strong binding was localized to the endometrial blood vessels. At the interface between maternal and fetal tissue, a similar pattern was observed whereby the numerous small capillaries at the bases of the two apposed epithelia bound vascular endothelial growth factor specifically. It is concluded that vascular endothelial growth factor produced by the maternal and fetal epithelial layers promotes the growth of capillaries locally, which would facilitate the development of two vascular networks for the efficient transfer of nutrients and waste products.

scholarly journals Ribosomal S6 Kinase as a Mediator of Keratinocyte Growth Factor-induced Activation of Akt in Epithelial Cells

2004 ◽  
Vol 15 (7) ◽  
pp. 3106-3113 ◽  
Author(s):  
Zhong-Zong Pan ◽  
Yvan Devaux ◽  
Prabir Ray
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Keratinocyte Growth Factor ◽  
Growth Factor Receptor ◽  
Protective Effects ◽  
S6 Kinase ◽  
Akt Activation ◽  
Ribosomal S6 Kinase

The keratinocyte growth factor receptor (KGFR) is a member of the fibroblast growth factor receptor (FGFR) superfamily. The proximal signaling molecules of FGFRs are much less characterized compared with other growth factor receptors. Using the yeast two-hybrid assay, we have identified ribosomal S6 kinase (RSK) to be a protein that associates with the cytoplasmic domain of the KGFR. The RSK family of kinases controls multiple cellular processes, and our studies for the first time show association between the KGFR and RSK. Using a lung-specific inducible transgenic system we have recently demonstrated protective effects of KGF on the lung epithelium and have demonstrated KGF-induced activation of the prosurvival Akt pathway both in vivo and in vitro. Here we show that a kinase inactive RSK mutant blocks KGF-induced Akt activation and KGF-mediated inhibition of caspase 3 activation in epithelial cells subjected to oxidative stress. It was recently shown that RSK2 recruits PDK1, the kinase responsible for both Akt and RSK activation. When viewed collectively, it appears that the association between the KGFR and RSK plays an important role in KGF-induced Akt activation and consequently in the protective effects of KGF on epithelial cells.

Mesenchymal transition in kidney collecting duct epithelial cells

2008 ◽  
Vol 294 (5) ◽  
pp. F1238-F1248 ◽  
Author(s):  
Larissa Ivanova ◽  
Michael J. Butt ◽  
Douglas G. Matsell
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Collecting Duct ◽  
Smooth Muscle Actin ◽  
Organ Damage ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
E Cadherin

Progressive organ damage due to tissue scarring and fibrosis is a paradigm shared by numerous human diseases including chronic kidney disease. The purpose of this study was to confirm the hypothesis that collecting duct (CD) epithelial cells can undergo mesenchymal transition (EMT) in vitro. The mechanism by which CDs undergo EMT is complex and involves both early and late cellular events. Early events include rapid insulin-like growth factor (IGF)-induced Akt and GSK-3β phosphorylation, associated with early disruption of E-cadherin-β-catenin membrane colocalization, with translocation of E-cadherin to endosomes, with translocation of β-catenin to the nucleus, and with an increase in Snail expression. Transforming growth factor-β1, on the other hand, induced early activation of Smad3 and its translocation to the nucleus, Erk1/2 phosphorylation, and early disruption of membrane E-cadherin localization. The late consequences of these events included a phenotypic transformation of the cells to a mesenchymal morphology with associated increase in vimentin and α-smooth muscle actin protein expression and a decrease in total cellular E-cadherin expression, detectable as early as 24 h after stimulation.

Keratinocyte growth factor stimulates bronchial epithelial cell proliferation in vitro and in vivo

1999 ◽  
Vol 277 (4) ◽  
pp. L737-L742 ◽  
Author(s):  
Peter H. Michelson ◽  
Margaret Tigue ◽  
Ralph J. Panos ◽  
Peter H. S. Sporn
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Keratinocyte Growth Factor ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial Cells ◽  
Brdu Incorporation ◽  
Bronchial Epithelial

Airway epithelial cell (AEC) proliferation is crucial to the maintenance of an intact airway surface and the preservation of host defenses. The factors that regulate AEC proliferation are not known. Keratinocyte growth factor (KGF), also known as FGF-7, is a member of the fibroblast growth factor family and a known epithelial cell mitogen. We studied the influence of KGF on the growth of cultured human bronchial epithelial cells and on bronchial cells of rats treated with KGF in vivo. First, we demonstrated the mRNA for the KGF receptor (KGFR) in both normal human bronchial epithelial (NHBE) cells and BEAS-2B cells (a human bronchial epithelial cell line). KGF caused a dose-dependent increase in DNA synthesis, as assessed by thymidine incorporation, in both cell types, with a maximal twofold increase in NHBE cells after 50 ng/ml KGF ( P < 0.001). KGF also induced a doubling in NHBE cell number at 10 ng/ml ( P < 0.001). Finally, we determined the effect of intratracheal administration of KGF to rats on proliferation of AEC in vivo. Measuring bromodeoxyuridine (BrdU) incorporation in AEC nuclei, KGF increased BrdU labeling of rat AEC in both large and small airways by approximately threefold compared with PBS-treated controls ( P < 0.001). Thus KGF induces proliferation of bronchial epithelial cells both in vitro and in vivo.

scholarly journals Co-localization of EGF transcripts and peptides by combined immunohistochemistry and in situ hybridization.

1990 ◽  
Vol 38 (12) ◽  
pp. 1853-1857 ◽  
Author(s):  
R I Couwenhoven ◽  
W Luo ◽  
M L Snead
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Simultaneous Detection ◽  
Interstitial Cells ◽  
Glandular Epithelium ◽  
Messenger Rnas ◽  
Tissue Sections ◽  
Representative Model ◽  
Epidermal Growth

There is increasing evidence that autocrine- and paracrine-acting growth factors participate in cell and tissue development, maintenance, and renewal. Recent advances in histochemical techniques have facilitated the localization of growth factor messenger RNAs or polypeptides in tissue sections. However, the spatial relationships between the sites of growth factor transcription, translation, and post-translational processing to functional bioactive peptides have been difficult to correlate because each method of detection requires separate tissue sections. We undertook the simultaneous detection of epidermal growth factor (EGF) transcripts and EGF epitopes by combining immunohistochemistry methods with in situ hybridization. Adult mouse submandibular gland was chosen as a representative model because it contains sites of EGF biosynthesis which may participate in mediating the development, maintenance, and renewal of the organ through autocrine or paracrine mechanism(s). Granular duct (GD) cells demonstrated the presence of both EGF transcripts and EGF peptides. In contrast, the interstitial cells lying adjacent to glandular epithelium also contained relatively high levels of EGF transcripts, although no mature EGF peptides were detected. The experimental approach of co-localization and the resulting data indicate previously unreported sites of EGF transcription in glandular interstitial cells, which may provide molecular information required for the morphogenesis and differentiation of adjacent glandular epithelium.

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