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Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy

Mazen Al-Essa1, Gursev S Dhaunsi1

  • 1Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait, Kuwait.

Journal of Pediatric Endocrinology & Metabolism : JPEM
|June 14, 2019
PubMed

Insights

Neonatal adrenoleukodystrophy (n-ALD) and X-linked ALD (X-ALD) patients show impaired growth factor activity, particularly reduced insulin-like growth factor-1 (IGF-1) function. This study investigates growth factor responses in patient fibroblasts, revealing distinct differences between n-ALD and X-ALD.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Genetics

Background:

  • Neonatal adrenoleukodystrophy (n-ALD) and X-linked ALD (X-ALD) are characterized by demyelination, poor growth, and cognitive decline.
  • Growth factors are crucial for pediatric development, and their dysregulation may contribute to ALD pathologies.

Purpose of the Study:

  • To investigate the mitogenic activity of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1) in skin fibroblasts from n-ALD and X-ALD patients.
  • To compare growth factor receptor expression and serum levels between ALD patients and healthy controls.

Main Methods:

  • Skin fibroblast cultures from n-ALD, X-ALD patients, and controls were stimulated with PDGF, bFGF, or IGF-1.
  • DNA synthesis was assessed via 5-bromo-2'-deoxyuridine (BrdU) incorporation.
  • Receptor expression (PDGF, bFGF, IGF-1) was analyzed by western blotting, and serum IGF-1 levels were measured using ELISA.

Main Results:

  • Fibroblasts from n-ALD and X-ALD patients exhibited significantly reduced DNA synthesis in response to fetal bovine serum (FBS).
  • The mitogenic effects of PDGF, bFGF, and IGF-1 were significantly lower in n-ALD cells compared to controls and X-ALD cells.
  • X-ALD cells showed impaired IGF-1-induced DNA synthesis. Reduced FGF receptor expression was noted in n-ALD cells. Both n-ALD and X-ALD patients had significantly lower serum IGF-1 levels and IGF-1 receptor expression.

Conclusions:

  • Growth factor activity is differentially affected in n-ALD and X-ALD.
  • A marked impairment of IGF-1 function, associated with receptor down-regulation, is evident in both n-ALD and X-ALD patients.

Keywords:
IGF-1growth factor receptorperoxisomal disorders

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