Expression and localization of FGFR1, FGFR2 and CTGF during normal human lung development

Anita Kolobaric; Katarina Vukojevic; Svjetlana Brekalo; Josip Misković; Mihael Ries; Lidija Lasic Arapovic; Violeta Soljic

doi:10.1016/j.acthis.2021.151719

Expression and localization of FGFR1, FGFR2 and CTGF during normal human lung development

Acta Histochem. 2021 Jul;123(5):151719. doi: 10.1016/j.acthis.2021.151719. Epub 2021 May 4.

Authors

Anita Kolobaric¹, Katarina Vukojevic², Svjetlana Brekalo³, Josip Misković⁴, Mihael Ries⁵, Lidija Lasic Arapovic⁶, Violeta Soljic⁶

Affiliations

¹ Department of Pediatrics, School of Medicine, University Hospital Center Mostar, Bijeli Brijeg bb, 88000, Mostar, Bosnia and Herzegovina; Department of Histology and Embryology, School of Medicine, University of Mostar, Bijeli Brijeg bb, 88000, Mostar, Bosnia and Herzegovina.
² Department of Histology and Embryology, School of Medicine, University of Mostar, Bijeli Brijeg bb, 88000, Mostar, Bosnia and Herzegovina; Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000, Split, Croatia. Electronic address: katarina.vukojevic@mefst.hr.
³ Department of Ophtalmology, University Hospital Center Mostar, Bijeli brijeg bb, 88000, Mostar, Bosnia and Herzegovina.
⁴ Department of Surgery, University Hospital Center Mostar, Bijeli brijeg bb, 88000, Mostar, Bosnia and Herzegovina.
⁵ Department of Otorhinolaryngology and Head and Neck Surgery, Sestre Milosrdnice University Hospital Centre, School of Medicine, University of Zagreb, Zagreb, Croatia.
⁶ Department of Histology and Embryology, School of Medicine, University of Mostar, Bijeli Brijeg bb, 88000, Mostar, Bosnia and Herzegovina.

PMID: 33962151
DOI: 10.1016/j.acthis.2021.151719

Abstract

Aim of our study was to provide insight into the temporal and spatial expression of FGFR1, FGFR2 and CTGF during normal human lung development which may have an important impact on understanding occurrence of developmental lung anomalies. Morphological parameters were analysed using double immunofluorescence on human embryonal (6th and 7th developmental week-dw) and foetal (8th, 9th and 16th developmental week) human lung samples. FGFR1 and FGFR2 was positive during all the dw in both the epithelium and mesenchyme. The highest number of FGFR1 positive cells was observed during the 6th dw (112/mm²) and 9th dw (87/mm²) in the epithelium compared to the 7th, 8th and 16th dw (Kruskal-Wallis test, p < 0.001, p < 0.0001). The highest number of FGFR1 positive cells in the mesenchyme was observed during the 8th dw (19/mm²) and 16th dw (13/mm²) compared to the 6th, 7th, and 9th dw (Kruskal-Wallis test, p < 0.001, p < 0.0001). The number of FGFR1 positive cells in the epithelium was higher for FGFR2 compared to number of positive cells (Mann-Whitney test, p < 0.0001). FGFR2 showed the highest number in the epithelium during the 7th dw (111/mm²) and 9th dw (87/mm²) compared to 6th, 8th and 16th dw (Kruskal-Wallis test, p < 0.001, p < 0.0001, p < 0.01 respectively). The highest number of FGFR2 positive cells in the mesenchyme was observed during the 9th dw (26/mm²), compared to the 6th, 7th,8th and 16th dw (Kruskal-Wallis test, p < 0.0001), while the number of FGFR2 positive cells in the epithelium was significantly higher than in the mesenchyme (Mann-Whitney test, p < 0.0001). CTGF was negative in both epithelium and mesenchyme during all except the 16th dw in the mesenchyme where it co-localized with FGFR2. FGFR1 and FGFR2 might be essential for epithelial-mesenchymal interactions that determine epithelial branching and mesenchymal growth during early lung development. Sudden increase in FGF1 in the epithelium and FGF2 in the mesenchyme in the foetus at 9th dw could be associated with the onset of foetal breathing movements. CTGF first appear during the foetal lung development.

Keywords: CTGF; Development; FGFR1; FGFR2; Lung.

MeSH terms

Connective Tissue Growth Factor / biosynthesis*
Epithelial-Mesenchymal Transition
Epithelium
Fluorescent Antibody Technique
Gene Expression
Gene Expression Regulation, Developmental*
Humans
Lung / embryology*
Mesoderm
Microscopy, Fluorescence
Receptor, Fibroblast Growth Factor, Type 1 / biosynthesis*
Receptor, Fibroblast Growth Factor, Type 2 / biosynthesis*

Substances

CCN2 protein, human
Connective Tissue Growth Factor
FGFR1 protein, human
FGFR2 protein, human
Receptor, Fibroblast Growth Factor, Type 1
Receptor, Fibroblast Growth Factor, Type 2