Elevated gene expression of MMP-1, MMP-10, and TIMP-1 reveal changes of molecules involved in turn-over of extracellular matrix in cyclosporine-induced gingival overgrowth

• Verfasst von: Dannewitz, Bettina [VerfasserIn]
• Verfasst von: Edrich, Christina [VerfasserIn]
• Verfasst von: Tomakidi, Pascal [VerfasserIn]
• Verfasst von: Kohl, Annette [VerfasserIn]
• Verfasst von: Gabbert, Olaf [VerfasserIn]
• Verfasst von: Eickholz, Peter [VerfasserIn]
• Verfasst von: Steinberg, Thorsten [VerfasserIn]
• Titel: Elevated gene expression of MMP-1, MMP-10, and TIMP-1 reveal changes of molecules involved in turn-over of extracellular matrix in cyclosporine-induced gingival overgrowth
• Verf.angabe: Bettina Dannewitz, Christina Edrich, Pascal Tomakidi, Annette Kohl, Olaf Gabbert, Peter Eickholz, Thorsten Steinberg
• E-Jahr: 2006
• Jahr: 3 May 2006
• Umfang: 10 S.
• Fussnoten: Gesehen am 10.02.2021
• Titel Quelle: Enthalten in: Cell & tissue research
• Ort Quelle: Berlin : Springer, 1924
• Jahr Quelle: 2006
• Band/Heft Quelle: 325(2006), 3, Seite 513-522
• ISSN Quelle: 1432-0878
• DOI: doi:10.1007/s00441-006-0200-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1747983241

Abstract

In humans, pathogenesis in cyclosporine A (CsA)-induced gingival overgrowth (GO) includes the accumulation of extracellular matrix (ECM) constituents, viz., collagen type-1 and type-3 and proteoglycans, in subgingival connective tissue. However, whether this increase is associated with alterations of molecules pivotal for the turn-over of collagens and proteoglycans remains unclear. The present study explores the status of matrix metalloproteinase MMP-1 and MMP-10, which are important for fibrillar collagen and proteoglycan turn-over, and their tissue inhibitor TIMP-1, on their gene expression and protein levels in frozen sections derived from GO and matched normal tissue. In situ hybridization (ISH) revealed elevated levels of MMP-1 gene expression in the connective tissue of GO compared with normal tissue. This elevation also applied to MMP-10 and TIMP-1, the latter exhibiting the strongest gene transcription in the deep connective tissue. These differences detected by ISH were corroborated by quantitative reverse transcription/polymerase chain reaction; relative gene expression analysis indicated a 1.9-fold increase for MMP-1, a 2.3-fold increase for MMP-10, and a 4.8-fold increase for TIMP-1. Detection of the protein by indirect immunofluorescence showed that normal gingival tissue was devoid of all three proteins, although they were detectable in GO tissue, with emphasis on TIMP-1. Analysis of our data indicates elevated levels of MMP-1 and-10, and particularly TIMP-1. With respect to TIMP-1, this elevation may in turn lead to alterations in ECM turn-over by abrogating MMP-1 and MMP-10, thereby contributing to ECM accumulation associated with GO.