Barx1, growth factors and apoptosis in facial tissue of children with clefts.
OBJECTIVE
Clefts of lip and palate belong to the most common birth defects worldwide. Growth factors and genes play an important role in tissue growth, differentiation and induction and upregulation of growth factors, apoptosis and matrix metalloproteinases might be involved in pathogenesis of facial clefts. The aim of this study was investigation of palate tissue in children with unilateral cleft lip palate for detection of local tissue growth factors, barx1 and apoptosis.


METHODS
We investigated soft and hard palate tissue from 36 children with complete unilateral cleft lip and palate from cleft area.14 children were in age before and primary dentition, but 22 children were in mixed dentition period. We examined the localization of barx1, FGFR1, NGFR, TGFbeta, BMP2/4, MMP2, PGP 9,5 by immunohistochemistry. TUNEL method was performed for detection of apoptotic cells.


RESULTS
Abundance of FGFR1 positive cells was seen almost in all cases. FGFR richly stained cells of soft and hard palate tissue. Abundance of NGFR positive cells was detected in basal epithelium, hair follicles, nerve fibers in wall of blood vessels and subepithelium, and was more often seen in children before mixed dentition. TGFbeta has showed intensive expression in epithelium, cartilage and bone in both dentition ages. Chondrocytes, fibroblasts and macrophages expressed MMP2 predominant before mixed dentition. Regional expression of barx1 was observed in epithelium before the mixed dentition, while during mixed dentition gene appeared in hyaline cartilage. TUNEL discovered apoptosis in both dentition ages.


CONCLUSIONS
FGFR1 and TGFbeta are main tissue stimulating growth factors in both dentition ages. Expression of barx1 appears in cleft lip palate affected structures mainly in mixed dentition ages. NGFR and neuropeptides-containing structures are mainly characteristic in cleft tissue before mixed dentition. Distribution of genes, GF and apoptosis seem to correlate rather with dentition age than to type of CLP.
Krivicka-Uzkurele
Benita
B
Institute of Anatomy and Anthropology, Riga Stradins University, 9 Kronvalda boulevard, Riga, Latvia, LV-1010. b.krivicka@inbox.lv
Pilmane
Mara
M
Akota
Ilze
I
D000367:Age Factors; D017209:Apoptosis / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000032:analysis; D002356:Cartilage / Q000473:pathology; D002648:Child; D019902:Chondrocytes / Q000473:pathology; D002971:Cleft Lip / Q000473:pathology*; D002972:Cleft Palate / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D018859:Hair Follicle / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D051457:Hyaline Cartilage / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008264:Macrophages / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D009412:Nerve Fibers / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis; D021362:Palate, Hard / Q000473:pathology; D010160:Palate, Soft / Q000473:pathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis; D043222:Ubiquitin Thiolesterase / Q000032:analysis
C490667:BARX1 protein, human; C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C482860:UCHL1 protein, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D043222:Ubiquitin Thiolesterase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2