Differential growth factor-induced modulation of proteoglycans synthesized by normal human renal versus cyst-derived cells.

In polycystic kidney disease (PKD), there is an insiduous enlargement of the kidneys and dilation of the renal tubules associated with extracellular matrix (ECM) alterations. The latter include thickening of tubular basement membrane and decreased synthesis of sulfated proteoglycan (PG). Because PKD is believed to be a disorder of cell growth and deranged ECM metabolism, it is conceivable that the formation of cystic tubules may be modulated by certain growth factors (GF) that influence the synthesis of ECM glycoproteins. In this study, the effect of various GF, i.e., epidermal, hepatocyte (HGF) and transforming (TGF), and triiodothyronine on the PG synthesized by normal human kidney (NK) epithelial cells and cells derived from cysts of patients with autosomal dominant PKD (ADPKD) was assessed. (35S) sulfate incorporation studies revealed that, among various GF, HGF and TGF-beta 1 had the maximal stimulatory effect on the synthesis of PG extracted from ADPKD cells. A minimal increase in the PG synthesis was observed in NK cells; however, PG synthesized under the influence of HGF or TGF-beta 1 were of relatively higher molecular weight, with a shift of K(av) from 0.28 to 0.12, as ascertained by Sepharose-6B chromatography. PG synthesized by ADPKD cells had a K(av) = 0.18, and it did not change with the GF treatment. The charge-density characteristics of PG of ADPKD cells were relatively lower than those of NK cells, and they were unaffected by HGF or TGF-beta 1 treatment. Interestingly, both the HGF and TGF-beta 1 significantly affected posttranslational modifications of PG.(ABSTRACT TRUNCATED AT 250 WORDS)

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Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling

AJP Renal Physiology ◽

10.1152/ajprenal.00285.2006 ◽

2007 ◽

Vol 292 (3) ◽

pp. F930-F945 ◽

Cited By ~ 91

Author(s):

Chang Xu ◽

Sandro Rossetti ◽

Lianwei Jiang ◽

Peter C. Harris ◽

Ursa Brown-Glaberman ◽

...

Keyword(s):

Epithelial Cells ◽

Nk Cells ◽

Coiled Coil ◽

Human Kidney ◽

Coiled Coil Domain ◽

Normal Human Kidney ◽

Cyst Cells ◽

Localization Signal ◽

Normal Human ◽

Autosomal Dominant Polycystic Kidney

Autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 (PC1) and polycystin-2 (PC2) colocalize in the apical monocilia of renal epithelial cells. Mouse and human renal cells without PC1 protein show impaired ciliary mechanosensation, and this impairment has been proposed to promote cystogenesis. However, most cyst epithelia of human ADPKD kidneys appear to express full-length PC1 and PC2 in normal or increased abundance. We show that confluent primary ADPKD cyst cells with the novel PC1 mutation ΔL2433 and with normal abundance of PC1 and PC2 polypeptides lack ciliary PC1 and often lack ciliary PC2, whereas PC1 and PC2 are both present in cilia of confluent normal human kidney (NK) epithelial cells in primary culture. Confluent NK cells respond to shear stress with transient increases in cytoplasmic Ca2+ concentration ([Ca2+]i), dependent on both extracellular Ca2+ and release from intracellular stores. In contrast, ADPKD cyst cells lack flow-sensitive [Ca2+]i signaling and exhibit reduced endoplasmic reticulum Ca2+ stores and store-depletion-operated Ca2+ entry but retain near-normal [Ca2+]i responses to ANG II and to vasopressin. Expression of wild-type and mutant CD16.7-PKD1(115–226) fusion proteins reveals within the COOH-terminal 112 amino acids of PC1 a coiled-coil domain-independent ciliary localization signal. However, the coiled-coil domain is required for CD16.7-PKD1(115–226) expression to accelerate decay of the flow-induced Ca2+ signal in NK cells. These data provide evidence for ciliary dysfunction and polycystin mislocalization in human ADPKD cells with normal levels of PC1.

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LOCALIZATION OF UROMUCOID IN HUMAN KIDNEY AND IN SECTIONS OF HUMAN KIDNEY STONE WITH THE FLUORESCENT ANTIBODY TECHNIQUE

Journal of Histochemistry & Cytochemistry ◽

10.1177/13.3.155 ◽

1965 ◽

Vol 13 (3) ◽

pp. 155-160 ◽

Cited By ~ 16

Author(s):

H. J. KEUTEL

Keyword(s):

Kidney Stones ◽

Kidney Stone ◽

Fluorescent Antibody ◽

Human Kidney ◽

Fluorescent Antibody Technique ◽

Renal Tubules ◽

Antibody Technique ◽

The Matrix ◽

Normal Human ◽

The Common

Fluorescent labeled antibodies were used for the demonstration of uromucoid. This urine specific mucoprotein is demonstrably present only in the epithelial cells of the proximal segments of the normal human renal tubules and in the matrix of human kidney stones of all the common crystalline compositions.

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Study of the Normal Human Kidney and Kidney Cancer with Monoclonal Antibodies

Uremia Investigation ◽

10.3109/08860228409115852 ◽

1984 ◽

Vol 8 (3-4) ◽

pp. 263-273 ◽

Cited By ~ 4

Author(s):

Neil H. Bander

Keyword(s):

Monoclonal Antibodies ◽

Kidney Cancer ◽

Human Kidney ◽

Normal Human Kidney ◽

Normal Human

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Biosynthesis of Complement C4 Messenger RNA in Normal Human Kidney

Nephron ◽

10.1159/000185778 ◽

1989 ◽

Vol 53 (4) ◽

pp. 338-342 ◽

Cited By ~ 26

Author(s):

H.E. Feucht ◽

J. Zwirner ◽

D. Bevec ◽

Margot Lang ◽

E. Felber ◽

...

Keyword(s):

Messenger Rna ◽

Human Kidney ◽

Complement C4 ◽

Normal Human Kidney ◽

Normal Human

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Different expression of the plasminogen activation system in renal thrombotic microangiopathy and the normal human kidney

Kidney International ◽

10.1038/ki.1996.523 ◽

1996 ◽

Vol 50 (6) ◽

pp. 2011-2019 ◽

Cited By ~ 45

Author(s):

Yichun Xu ◽

Jacqueline Hagege ◽

Béatrice Mougenot ◽

Jean-Daniel Sraer ◽

Ebbe Rønne ◽

...

Keyword(s):

Thrombotic Microangiopathy ◽

Human Kidney ◽

Plasminogen Activation ◽

Plasminogen Activation System ◽

Normal Human Kidney ◽

Activation System ◽

Normal Human

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TOXOHORMONE IN BACTERIA-FREE TUMORS

Canadian Journal of Biochemistry ◽

10.1139/o66-124 ◽

1966 ◽

Vol 44 (8) ◽

pp. 1069-1087 ◽

Cited By ~ 1

Author(s):

J. C. Nixon ◽

B. Zinman

Keyword(s):

Gel Filtration ◽

Human Kidney ◽

Metastatic Carcinoma ◽

Exchange Chromatography ◽

Human Spleen ◽

Normal Tissues ◽

Highly Active ◽

Normal Human Kidney ◽

Tumor Tissues ◽

Normal Human

Toxohormone was extracted from bacteria-free human tumors and normal tissues, and assayed for activity by measuring the decrease in serum iron levels of rats 12 hours after injection of the extracts. In contrast with the findings of others, the results of the present study demonstrated that active toxohormone could be isolated from bacteria-free tumor tissues. Bacteria-free normal human kidney and spleen also yielded active toxohormone extracts, whereas extracts of normal human- and rat-skeletal muscle and rat liver had no activity.Four active toxohormone extracts were purified by ion-exchange chromatography followed by gel filtration. Human leukemic spleen, metastatic carcinoma of the cecum, and normal human spleen and kidney yielded several highly active purified fractions.

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