Thesis (doctoral)--München, 1983.

Regensburg, Univ., Diss., 2008

Made available in DSpace on 2015-03-03T15:38:43Z (GMT). No. of bitstreams: 1 PedroPAS_TESE_1-70.pdf: 4719637 bytes, checksum: 8f16cb0e2326a80cfc947b1ea2b89641 (MD5) Previous issue date: 2012-02-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Myofibroblasts are cells that exhibit a hybrid phenotype, sharing the morphological characteristics of fibroblasts and smooth muscle cells, which is acquired during a process called differentiation. These cells then start to express -SMA, a marker that can be used for their identification. Studies suggest that myofibroblasts are related to the aggressiveness of different tumors and that TGF-1 and IFN- play a role in myofibroblast differentiation, stimulating or inhibiting this differentiation, respectively. The objective of this study was to investigate the role of myofibroblasts in epithelial odontogenic tumors, correlating the presence of these cells with the aggressiveness of the tumor. Immunohistochemistry was used to evaluate the expression of TGF-1 and IFN- in myofibroblast differentiation, as well as the expression of MMP-13, which is activated by myofibroblasts, and of EMMPRIN (extracellular matrix metalloproteinase inducer) as a precursor of this MMP. The sample consisted of 20 solid ameloblastomas, 10 unicystic ameloblastomas, 20 odontogenic keratocysts, and 20 adenomatoid odontogenic tumors. For evaluation of myofibroblasts, anti- -SMA-immunoreactive cells were quantified in connective tissue close to the epithelium. Immunoexpression of TGF-1, IFN-, MMP-13 and EMMPRIN was evaluated in the epithelial and connective tissue components, attributing scores of 0 to 4. The results showed a higher concentration of myofibroblasts in solid ameloblastomas (mean of 30.55), followed by odontogenic keratocysts (22.50), unicystic ameloblastomas (20.80), and adenomatoid odontogenic tumors (19.15) (p=0.001). No significant correlation between TGF-1 and IFN- was observed during the process of myofibroblast differentiation. There was also no correlation between the quantity of myofibroblasts and MMP-13 expression. Significant correlations were found between MMP-13 and TGF-1 (r=0.087; p=0.011), between MMP- 13 and IFN- (r=0.348; p=0.003), as well as between EMMPRIN and MMP-13 (r=0.474; p<0.001) and between EMMPRIN and IFN- (r=0.393; p=0.001). The higher quantity of myofibroblasts observed in solid ameloblastomas, odontogenic keratocysts and unicystic ameloblastomas suggests that these cells are one of the factors responsible for the more aggressive biological behavior of these tumors, although the myofibroblast population was not correlated with TGF-1, IFN-, MMP-13 or EMMPRIN. The correlation between MMP- 13 and TGF-1 suggests that the latter induces the expression of this metalloproteinase. The present results also support the well-established role of EMMPRIN as an inducer of MMP-13. Furthermore, the relationship between EMMPRIN and IFN- and between MMP-13 and IFN- suggests synergism in the antifibrotic effect of these markers / Os miofibroblastos s?o c?lulas que apresentam um fen?tipo h?brido exibindo caracter?sticas morfol?gicas de fibroblastos e de c?lulas musculares lisas, sendo a aquisi??o de tal fen?tipo denominada diferencia??o, passando ent?o a expressar a -SMA, a qual ? importante na identifica??o dessas c?lulas. Estudos t?m sugerido que os miofibroblastos apresentam rela??o com a agressividade de diversas les?es e que o seu processo de diferencia??o estaria relacionado ? express?o do TGF- 1 e do IFN- atuando, respectivamente, no est?mulo e na inibi??o dessa diferencia??o. O objetivo deste trabalho foi investigar o papel dos miofibroblastos em les?es odontog?nicas epiteliais, relacionando-os ? agressividade das les?es e analisar por meio da imuno-histoqu?mica, a express?o do TGF- 1 e IFN- no processo de diferencia??o, al?m da an?lise da MMP-13 que ? ativada por miofibroblastos e do indutor de metaloproteinases de matriz (EMMPRIN) como precursor desta MMP. A amostra foi constitu?da por 20 ameloblastomas s?lidos, 10 ameloblastomas unic?sticos, 20 ceratocistos odontog?nicos e 20 tumores odontog?nicos adenomat?ides. Para a avalia??o dos miofibroblastos, foram quantificadas as c?lulas imunorreativas ao anticorpo - SMA presentes no tecido conjuntivo, pr?ximo ao tecido epitelial. As express?es de TGF- 1, IFN- , MMP-13 e EMMPRIN, foram avaliadas no componente epitelial e no conjuntivo, estabelecendo-se o percentual de imunorreatividade e atribuindo-se escores de 0 a 4. A an?lise dos miofibroblastos evidenciou maior concentra??o nos ameloblastomas s?lidos (m?dia de 30,55), seguido pelos ceratocistos odontog?nicos (22,50), ameloblastomas unic?sticos (20,80) e tumores odontog?nicos adenomat?ides (19,15) com valor de p= 0,001. N?o foi encontrada correla??o significativa entre TGF- 1 e IFN- no processo de diferencia??o dos miofibroblastos, bem como na rela??o entre a quantidade de miofibroblastos e a express?o da MMP-13. Constatou-se, correla??o estat?stica entre MMP-13 e TGF- 1 (r= 0,087; p= 0,011) al?m de significante correla??o entre MMP-13 e IFN- (r=0,348; p=0,003). Entre EMMPRIN e MMP-13 verificou-se signific?ncia (r= 0,474; p<0,001) assim como entre EMMPRIN e IFN- (r=0,393; p=0,001). A maior quantidade de miofibroblastos evidenciada nos ameloblastomas s?lidos, ceratocistos odontog?nicos e ameloblastomas unic?sticos sugere que estas c?lulas podem ser um dos fatores respons?veis para um comportamento biol?gico mais agressivo destas les?es, embora a popula??o de miofibroblastos n?o tenha apresentado correla??o com TGF- - 1, IFN- ,MMP-13 e EMMPRIN. Quanto a correla??o evidenciada entre MMP-13 e TGF- 1, isto pode sugerir um papel indutor do TGF- 1 para a express?o da MMP-13, assim como os resultados deste estudo refor?am a rela??o bem estabelecida do EMMPRIN como indutor da MMP-13. Constatou-se tamb?m rela??o entre EMMPRIN e IFN- assim como entre MMP-13 e IFN- sugerindo, dessa forma, um sinergismo na a??o anti-fibr?tica desses marcadores