Possible Role of WT1 in a Human Fetus with Evolving Bronchial Atresia, Pulmonary Malformation and Renal Agenesis

Author:

Loo Christine K.C.123,Algar Elizabeth M.4,Payton Diane J.1,Perry-Keene Joanna1,Pereira Tamara N.2,Ramm Grant A.2

Affiliation:

1. Department of Anatomical Pathology, Royal Brisbane and Women's Hospital, Brisbane, Australia

2. Hepatic Fibrosis Group, Queensland Institute of Medical Research, Brisbane, Australia

3. Discipline of Pathology, School of Medicine, University of Western Sydney, NSW, Australia

4. Molecular Oncology Laboratory, Murdoch Children's Research Institute and University of Melbourne Dept of Paediatrics, Royal Children's Hospital, Flemington Rd, Parkville, Melbourne, Australia

Abstract

The association of peripheral bronchial atresia and congenital pulmonary airway malformation (CPAM) has recently been recognised, but the pathology of the lesions evolving together has not been described. We present autopsy findings in a 20 week fetus showing areas of peripheral bronchial destruction and airway malformation consistent with developing CPAM in the right lung supporting a causal relationship between these lesions. This fetus also had congenital heart defect, bilateral renal agenesis and syndactyly. We identified another fetus from our autopsy files, with bilateral renal agenesis, similar right sided pulmonary malformation and cardiac defects. Similar bilateral renal agenesis and defects of the heart and lungs are found in wt1−-/–mice and we have investigated the expression of WT1 in these fetuses. We hypothesise that the cardiac, liver, renal and possibly lung lesions in these two cases may arise due to mesenchymal defects consequent to WT1 misexpression and discuss evidence for this from the scientific literature. We used immunoperoxidase stains to analyse WT1 expression in autopsy hepatic tissue in both fetuses. We also investigated the expression of α-smooth muscle actin (α-SMA), a marker of activated hepatic stellate cells/myofibroblasts, and desmin in hepatic mesenchyme and compare these findings with control fetuses, without congenital malformations. We found reduced WT1 expression in hepatic mesothelium in both fetuses with malformations. There was also increased expression of α-SMA in liver perisinusoidal cells, as seen in the wt1−-/–mouse model. We therefore propose that abnormality of WT1 signalling may be an underlying factor, as WT1 is expressed in coelomic lining cells from which mesenchyme is derived in many organs.

Publisher

SAGE Publications

Subject

General Medicine,Pathology and Forensic Medicine,Pediatrics, Perinatology, and Child Health

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