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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
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/18671 |
| Date | 28 February 2012 |
| Creators | Santos, Pedro Paulo de Andrade |
| Contributors | http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4787927Z7&dataRevisao=null, Santos, Jean Nunes dos, CPF:62627673487, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728907T1, Pinto, Le?o Pereira, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4787928A2, Freitas, Roseana de Almeida, CPF:28444361453, http://lattes.cnpq.br/9512014003639405, Martins, Manoela Domingues, CPF:61802611053, http://lattes.cnpq.br/4958184722611235, Souza, L?lia Batista de |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Patologia Oral, UFRN, BR, Odontologia |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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