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Doctoral Thesis
DOI
10.11606/T.42.2008.tde-09092008-132737
Document
Author
Full name
Ricardo Frota Boggio
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Santelli, Glaucia Maria Machado (President)
Ionta, Marisa
Jaeger, Ruy Gastaldoni
Mathor, Monica Beatriz
Oliveira, Sergio Ferreira de
Title in Portuguese
Efeitos do bloqueador do canal de cálcio (Verapamil) sobre fibroblastos dérmicos humanos.
Keywords in Portuguese
Actina
Cálcio Citosólico
Colagenase
Colágeno
Fibroblastos humanos
Verapamil
Abstract in Portuguese
O excesso de tecido cicatricial (quelóides e cicatrizes hipertróficas) é um defeito do processo de cicatrização das feridas, caracterizado por um aumento na produção da matriz extracelular. Neste estudo, fibroblastos dérmicos humanos tratados com 50 mM verapamil apresentaram discreta modificação na distribuição dos microfilamentos e alteraram sua morfologia de fusiformes para estrelados/arredondados. Estes efeitos poderiam estar associados a baixos níveis de cálcio citosólico. Esta hipótese foi confirmada através marcação de fibroblastos tratados com calcium green. Observamos também, que o verapamil inibiu a proliferação celular em 64,4%, aumentou a secreção de MMP1 e diminuiu o colágeno sintetizado pelos fibroblastos, sem aparentes efeitos citotóxicos. O metabolismo celular do cálcio está aparentemente relacionado a produção da matriz extracelular e portanto as patologias hipertróficas da cicatrização (quelóides e cicatrizes hipertróficas) podem responder ao tratamento com bloqueadores do canal de cálcio (verapamil).
Title in English
Effects of calcium channel blocker (Verapamil) on human dermal fibroblasts.
Keywords in English
Actin
Collagen
Collagenase
Cytosolic calcium
Human fibroblasts
Verapamil
Abstract in English
Excessive scar tissue (keloids and hypertrophic scars) is a defective wound healing process characterized by overproduction of extracellular matrix. In the present study human dermal fibroblasts treated with 50 mM verapamil changed their normal spindle-shaped morphology to stellate/rounded and showed discrete reorganization of microfilaments We hypothesized that these effects would be associated to lower levels of cytosolic Ca2+. Indeed, short time loading with calcium green confirmed that verapamil-treated fibroblasts exhibited lower intracellular calcium levels. We also observed that verapamil decrease cellular proliferation by 64.4%, increase the secretion of MMP1 and decrease synthesis of collagen in cultured fibroblasts. This alterations induced by verapamil are not associated with cytotoxic effects. The cellular calcium metabolism appears to regulate extracellular matrix production and so those hypertrophic disorders of wound healing (keloids and hypertrophic scars) may respond to therapy with calcium antagonist drugs (verapamil).
 
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Publishing Date
2008-09-11
 
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