Role of follicle-stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease

Authors

  • Paolo Onori,

    1. Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome ‘Sapienza’, Rome, Italy
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  • Romina Mancinelli,

    1. Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome ‘Sapienza’, Rome, Italy
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  • Antonio Franchitto,

    1. Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome ‘Sapienza’, Rome, Italy
    2. Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy
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  • Guido Carpino,

    1. Department of Health Science, University of Rome ‘Foro Italico’, Rome, Italy
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  • Anastasia Renzi,

    1. Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome ‘Sapienza’, Rome, Italy
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  • Stefania Brozzetti,

    1. Department of Surgical Sciences, University of Rome ‘Sapienza’, Rome, Italy
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  • Julie Venter,

    1. Scott & White Digestive Disease Research Center, Central Texas Veterans Health Care System and Texas A&M Health Science Center, College of Medicine, Temple, TX, USA
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  • Heather Francis,

    1. Scott & White Digestive Disease Research Center, Central Texas Veterans Health Care System and Texas A&M Health Science Center, College of Medicine, Temple, TX, USA
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  • Shannon Glaser,

    1. Scott & White Digestive Disease Research Center, Central Texas Veterans Health Care System and Texas A&M Health Science Center, College of Medicine, Temple, TX, USA
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  • Douglas M. Jefferson,

    1. Department of Physiology, Tufts University, Boston, MA, USA
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  • Gianfranco Alpini,

    1. Scott & White Digestive Disease Research Center, Central Texas Veterans Health Care System and Texas A&M Health Science Center, College of Medicine, Temple, TX, USA
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  • Eugenio Gaudio

    Corresponding author
    • Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome ‘Sapienza’, Rome, Italy
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Correspondence

Professor Eugenio Gaudio, MD, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, ‘Sapienza’ University of Rome, Via A. Borelli, 50-00161 Rome, Italy

Tel: +39 06 4991 8060

Fax: +39 06 4991 8062

e-mail: eugenio.gaudio@uniroma1.it

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the progressive development of renal and hepatic cysts. Follicle-stimulating hormone (FSH) has been demonstrated to be a trophic factor for biliary cells in normal rats and experimental cholestasis induced by bile duct ligation (BDL).

Aims

To assess the effect of FSH on cholangiocyte proliferation during ADPKD using both in vivo and in vitro models.

Methods

Evaluation of FSH receptor (FSHR), FSH, phospho-extracellular-regulated kinase (pERK) and c-myc expression in liver fragments from normal patients and patients with ADPKD. In vitro, we studied proliferating cell nuclear antigen (PCNA) and cAMP levels in a human immortalized, non-malignant cholangiocyte cell line (H69) and in an immortalized cell line obtained from the epithelium lining the hepatic cysts from the patients with ADPKD (LCDE) with or without transient silencing of the FSH gene.

Results

Follicle-stimulating hormone is linked to the active proliferation of the cystic wall and to the localization of p-ERK and c-myc. This hormone sustains the biliary growth by activation of the cAMP/ERK signalling pathway.

Conclusion

These results showed that FSH has an important function in cystic growth acting on the cAMP pathway, demonstrating that it provides a target for medical therapy of hepatic cysts during ADPKD.

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