Keratinocytes modify fibroblast metabolism in hereditary gingival fibromatosis.
OBJECTIVE
Hereditary gingival fibromatosis (HGF) is a rare benign disorder characterized by progressive fibrous overgrowth of the gingiva. The proliferation and expression of growth factors of HGF keratinocytes are abnormal. However, the exact role of keratinocytes in HGF pathogenesis is still unknown. The present study aimed to clarify the interactions between HGF keratinocytes and underlying fibroblasts in the pathogenesis of HGF.


METHODS
Gingival tissues, fibroblasts and keratinocytes from three Chinese HGF patients and three healthy subjects were collected. Histological analyses were performed by histochemical and immunohistochemical staining (Ki-67). Gingival fibroblasts were cocultured with gingival keratinocytes in an in vitro coculture system. The mRNA levels of type I collagen, MMP-1, MMP-3, and TIMP-1 were analysed in the cocultured gingival fibroblasts by reverse-transcription polymerase chain reaction (RT-PCR). The production of type I collagen and TIMP-1 was examined by ELISA.


RESULTS
The number of Ki-67-positive keratinocytes in tissue sections from patients was higher than in those from controls. HGF fibroblasts cocultured with HGF keratinocytes showed an increased expression of type I collagen and TIMP-1. Transmission electron microscopy showed increased rough endoplasmic reticulum and ribosomes in cocultured HGF fibroblasts.


CONCLUSIONS
These results suggest that HGF keratinocytes have an important role in HGF pathogenesis by inducing extracellular matrix (ECM) accumulation by fibroblasts.
Meng
Liuyan
L
Key Laboratory for Oral Biomedical Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Luoyu Road 237, 430079 Wuhan, PR China.
Ye
Xiaoqian
X
Fan
Mingwen
M
Xiong
Xuepeng
X
Von den Hoff
Johannes W
JW
Bian
Zhuan
Z
D000293:Adolescent; D000328:Adult; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005351:Fibromatosis, Gingival / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D005881:Gingiva / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
D024042:Collagen Type I; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1