title: Proliferation, apoptosis and expression of matrix metalloproteinase-9 in human fetal lung.
abstract: Expression pattern of the Ki-67, caspase-3 and matrix metalloproteinases-9 (MMP-9) factors were immunohistochemically analyzed in 48 human fetal lungs from 12 to 40 weeks of gestation. The number of Ki-67 positive cells in the epithelium of canaliculare (88cells/mm(2)) and sacculare stage (93cells/mm(2)) were significantly higher than in the epithelium of pseudoglandular stage (12cells/mm(2)) (p=0.0008 vs. p=0.003). The number of Ki-67 positive cells in the mesenchyme of canaliculare stage (132cells/mm(2)) was significantly higher than in the mesenchyme of pseudoglandular stage (37cells/mm(2)) (p=0.001). The proliferation of mesenchymal cells was higher than the epithelial cells in all developmental stages, especially in the canaliculare stage (p=0.007). Similarly, the number of caspase-3 positive cells in the epithelium of canalicular stage (13cells/mm(2)) was significantly higher than in the epithelium of pseudoglandular stage (6cells/mm(2)) (p=0.002) with peaks in the conductive epithelium of canalicular stage. The number of caspase-3 positive cells in the mesenchyme of canaliculare stage (3cells/mm(2)) was significantly higher than in the mesenchyme of saccular stage (0cells/mm(2)) (p=0.05). There were no caspase-3 positive cells in the mesenchyme of pseudoglandular stage. However, unlike the Ki-67 expression, mesenchymal cells in comparison to epithelial cells express substantially less caspase-3 in all developmental stages. Up to the saccular stage, the expression of MMP-9 in mesenchymal cells showed a linear increase with most pronounced expression in that stage. The number of MMP-9 positive cells in the mesenchyme of canaliculare (20cells/mm(2)) and sacculare (39cells/mm(2)) stage were significantly higher than in the mesenchyme of pseudoglandular stage (12cells/mm(2)) (p=0.04 vs. p=0.004). The first epithelial cells that express MMP-9 were present only at the alveolar stage. Increased proliferation and apoptosis of the mesenchymal cells of canalicular stage is important for formation of definite structures within the stroma of the lung parenchyma. Although apoptosis in the epithelium is not pronounced as proliferation, it is important for thinning of the epithelium and consequent spread of respiratory tract. However in the saccular stage when mesenchyme disappears, MMP-9 expression is more important for primitive alveoli differentiation.
authors.affiliation: Department of pediatrics, University Hospital in Mostar, Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kraljevic
authors.affiliation: Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Soltanska 2, 21000 Split, Croatia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vukojevic
authors.affiliation: Department of Pathology, Cytology and Forensic Medicine, University Hospital in Mostar, Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Dragana
authors.initials: D
authors.lastname: Karan
authors.affiliation: Department of pediatrics, University Hospital in Mostar, Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Borko
authors.initials: B
authors.lastname: Rajic
authors.affiliation: Department of Pathology, Cytology and Forensic Medicine, University Hospital in Mostar, Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Jelena
authors.initials: J
authors.lastname: Todorovic
authors.affiliation: Department of Surgery, University Hospital in Mostar, Kralja Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Josip
authors.initials: J
authors.lastname: Miskovic
authors.affiliation: Department of Gynecology, University Hospital in Mostar, Kralja Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Vajdana
authors.initials: V
authors.lastname: Tomic
authors.affiliation: Laboratory of Morphology, Department of Histology and Embryology, School of Medicine, University of Mostar, Bijelibrijeg bb, 88000 Mostar, Bosnia and Herzegovina.
authors.forename: Mario
authors.initials: M
authors.lastname: Kordic
authors.affiliation: Department of Pathology, Cytology and Forensic Medicine, University Hospital in Mostar, Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina; Laboratory of Morphology, Department of Histology and Embryology, School of Medicine, University of Mostar, Bijelibrijeg bb, 88000 Mostar, Bosnia and Herzegovina. Electronic address: vsoljic@gmail.com.
authors.forename: Violeta
authors.initials: V
authors.lastname: Soljic
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology*
chemical_list: C505407:CASP3 protein, human; D053148:Caspase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Caspase-3; Fetal development; Ki-67; Lung; Matrix metalloproteinase-9; Proliferation