The role of hepatocyte growth factor in the humoral regulation of inguinal hernia closure.
BACKGROUND
Calcitonin gene-related peptide (CGRP) is proposed to indirectly cause inguinal hernia closure via hepatocyte growth factor (HGF). Studies have shown that CGRP and HGF cause processus vaginalis (PV) fusion in vitro. We localized the HGF receptor in the PV and tested whether CGRP was responsible for HGF release.


METHODS
Hernial sacs collected from 20 children (15 males, 4 females, 1 XY female) undergoing inguinal hernia repair were immunohistochemically stained for HGF receptor (c-met). Parietal peritoneum was stained for comparison. Hernial sacs from another 16 children (12 males, 4 females), with each sac divided into 4, were cultured, with and without CGRP, for 24 and 48 hours. Hepatocyte growth factor content was then assayed in the culture medium (4/16 children) and tissue extracts (12/16 children), using enzyme-linked immunosorbent assay. Children were aged 1 month to 10 years. Data were analyzed using paired Student t tests.


RESULTS
C-met localized to the PV epithelial surface in 17 of 20 hernial sacs and in the parietal peritoneum. Hepatocyte growth factor levels increased over time in 4 of 4 culture medium assays, with a significant difference in 1 of 4. Seven of 12 tissue extract assays had significant differences; however, 3 of 7 had decreased HGF levels.


CONCLUSIONS
The presence of HGF receptors in the PV is consistent with a role for HGF in triggering epithelial-mesenchymal transformation during inguinal hernia closure. The presence of HGF receptors in the parietal peritoneum suggests that regulation of this process is complex. Enzyme-linked immunosorbent assay results indicate that, in a subset of patients, exogenous CGRP may be responsible for HGF elevation and potentially implicates deficient endogenous CGRP as one cause for inguinal hernia patency.
Ting
Alvin Y S
AY
Department of Paediatrics, University of Melbourne, Melbourne 3050, Australia.
Huynh
Jenny
J
Farmer
Pamela
P
Yong
Eric X Z
EX
Hasthorpe
Suzanne
S
Fosang
Amanda
A
King
Sebastian
S
Deshpande
Aniruddha
A
Hutson
John
J
D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000196:embryology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000502:physiology*; D006552:Hernia, Inguinal / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008648:Mesoderm; D010537:Peritoneum / Q000196:embryology; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D015740:Calcitonin Gene-Related Peptide