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Increased expression of transforming growth factor-alpha in infantile hypertrophic pyloric stenosis
1Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin 12, Ireland.
Insights
Transforming growth factor-alpha (TGF-alpha) is elevated in infantile hypertrophic pyloric stenosis (IHPS). This growth factor likely drives the pyloric muscle thickening characteristic of IHPS.
Area of Science:
- Gastroenterology
- Developmental Biology
- Cell Biology
Background:
- Infantile hypertrophic pyloric stenosis (IHPS) involves pyloric muscle thickening.
- Smooth muscle cell (SMC) growth is influenced by growth factors like transforming growth factor-alpha (TGF-alpha).
- TGF-alpha is known to promote SMC growth in various tissues.
Purpose of the Study:
- To investigate the role of TGF-alpha in the pyloric muscle hypertrophy observed in IHPS.
- To determine if TGF-alpha expression is increased in IHPS pyloric muscle.
Main Methods:
- Pyloric muscle biopsy specimens from 10 IHPS patients and 10 age-matched controls.
- Indirect immunohistochemistry using anti-TGF-alpha antibody.
- In-situ hybridization with a TGF-alpha-specific oligonucleotide probe.
Main Results:
- Significantly increased TGF-alpha immunoreactivity in IHPS pyloric SMCs compared to controls.
- Markedly elevated TGF-alpha messenger RNA (mRNA) expression in IHPS pyloric SMCs.
- Evidence of increased local TGF-alpha synthesis by pyloric SMCs in IHPS.
Conclusions:
- Increased TGF-alpha expression and immunoreactivity suggest a key role in IHPS pathogenesis.
- TGF-alpha likely contributes to the pyloric muscle hypertrophy characteristic of IHPS.
- Findings highlight TGF-alpha as a potential therapeutic target for IHPS.
Abstract:
Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The growth of smooth-muscle cells (SMCs) is regulated by several growth factors. Transforming growth factor-alpha (TGF-alpha) is a growth-regulatory peptide found in a wide range of embryonic and adult tissues. It has been recognized that TGF-alpha has growth-promoting effects in vascular and visceral SMCs. The aim of this study was to investigate whether TGF-alpha plays a role in the pyloric-muscle hypertrophy in IHPS. Full-thickness pyloric-muscle biopsy specimens were obtained at the time of pyloromyotomy from 10 IHPS patients (age range 24-76 days). Age-matched control material included 10 pyloric-muscle specimens taken at autopsy in patients without evidence of gastrointestinal disease. Indirect immunohistochemistry was performed using the ABC method with anti-TGF-alpha polyclonal antibody. In-situ hybridization was performed using a digoxigenin-labelled, TGF-alpha-specific oligonucleotide probe. There was a marked increase in TGF-alpha immunoreactivity and messenger RNA (mRNA) expression in SMCs in pyloric circular and longitudinal muscle in IHPS specimens compared to controls. The increased expression of TGF-alpha mRNA together with increased TGF-alpha immunoreactivity in IHPS suggests increased local synthesis of TGF-alpha by pyloric SMCs, causing pyloric-muscle hypertrophy.