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Stimulating effect of growth hormone on type IV collagen production by endothelial cells cultured in normal and high glucose

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Abstract

Collagen IV accumulation is characteristic of diabetic angiopathy. To test the possible contribution of GH, we studied its effects on collagen IV production by human umbilical vein endothelial cells at 5.5 and 16.7 mmol/l glucose. GH (100 ng/ml) markedly increased collagen IV level in the culture supernatant and in the insoluble extracellular matrix and cell fraction at both glucose concentrations. This stimulating effect of GH was additional to that of high glucose. It was more pronounced on collagen IV than on total protein synthesis. GH increased free latent gelatinase activity slightly at normal and markedly at high glucose. Using GF109203X, a PKC inhibitor, we observed that high glucose, but not GH, activated PKC. These two factors stimulating collagen IV production appear to work through different pathways, favoring an additivity of their effects. This supports the contribution of high plasma GH in diabetic vascular basement membrane thickening.

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Abbreviations

APMA:

p Aminophenylmercuric acetate

BM:

Basement membrane

EC:

Endothelial cells

GH:

Growth hormone

hGH:

Human GH

bGH:

Bovine GH

HS:

Human serum

HUVEC:

Human umbilical vein EC

JAK2:

Janus kinase 2

M199:

199 culture medium

PKC:

Protein kinase C

PKCI:

PKC inhibitor

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Acknowledgments

This work was supported by the University of Paris V and VI and the “Fondation pour la Recherche Médicale”. We thank Dr H. Cohen and colleagues (Maternité, Hôpital International de l’Université de Paris) for providing us with umbilical cords; Pr C. Roussel, Pr J.P. Bisson and colleagues (Département de Biologie de la Reproduction, Faculté de Médecine des Saints-Pères) for cell culture facilities; Dr D. Hartmann (Institut Pasteur, Lyon) for providing us with anti-type IV collagen antiserum and various antigens; J. Kirilovsky (Glaxo) for his generous gift of GF109203X; Choay Laboratories for providing us with hGH; G.Mozère and G. Hirbec for technical help.

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Authors and Affiliations

  1. Equipe de Recherches sur la Biochimie et la Pharmacologie des Vaisseaux et du Rein, “Protéines Modifiées, Protéases et Physiopathologie de l’Endothélium Vasculaire”, Laboratoire de Pharmacologie, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006, Paris, France

    A. Bakillah, R. Guillot, P. Urios, A.-M. Grigorova-Borsos & M. Sternberg

  2. Laboratoire d’Hormonologie Pédiatrique et de Métabolisme Hôpital Saint-Vincent-de-Paul, 82 avenue Denfert-Rochereau, 75014, Paris, France

    M. Sternberg

  3. Laboratoire d’Hormonologie et de Génétique, Hôpital Bichat, Paris, France

    P. Urios

  4. Laboratoire de Biochimie et de Génétique Moléculaire, Hôpital Ambroise Paré, 92100, Boulogne, France

    A.-M. Grigorova-Borsos

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  1. A. Bakillah
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  2. R. Guillot
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  3. P. Urios
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  4. A.-M. Grigorova-Borsos
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  5. M. Sternberg
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Correspondence to M. Sternberg.

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Bakillah, A., Guillot, R., Urios, P. et al. Stimulating effect of growth hormone on type IV collagen production by endothelial cells cultured in normal and high glucose. Amino Acids 43, 697–707 (2012). https://doi.org/10.1007/s00726-011-1118-5

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  • DOI: https://doi.org/10.1007/s00726-011-1118-5

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