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Exogenous transforming growth factor‐β 2 enhances connective tissue formation in transforming growth factor‐β 1 —deficient, healing‐impaired dermal wounds in mice
Author(s) -
Ksander George A.,
Gerhardt Carolyn O.,
Olsen David R.
Publication year - 1993
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.1993.10303.x
Subject(s) - connective tissue , extracellular matrix , transforming growth factor , transforming growth factor beta , western blot , wound healing , endogeny , chemistry , extracellular , growth factor , microbiology and biotechnology , biology , pathology , endocrinology , immunology , biochemistry , medicine , gene , receptor
Connective tissue formation is markedly reduced in full‐thickness mouse dermal wounds that are covered with synthetic, adherent, moisture vapor—permeable membrane when compared with formation in similar but nonoccluded wounds. The transforming growth factors‐β (TGF‐β) are a family of multifunctional peptides thought to have a critical role in the regulation of development and tissue repair. Treatment with exogenous TGF‐β 1 stimulated connective tissue formation in wounds covered with synthetic, adherent, moisture vapor—permeable membrane but had no effect on air‐exposed wounds, suggesting that the quantity of endogenous TGF‐β 1 in wounds covered with synthetic, adherent, moisture vapor—permeable membrane was less than that in air‐exposed wounds. Immunolocalization studies with an anti‐TGF‐β 1 antibody confirmed that wounds covered with synthetic, adherent, moisture vapor—permeable membrane demonstrated markedly reduced levels of endogenous extracellular, matrix‐associated TGF‐β 1 as early as 24 hours after wounding. Immunoreactive TGF‐β 2 was not detected. These findings suggest that endogenous TGF‐β 1 , but not TGF‐β 2 , is required for normal connective tissue formation in this model and that impaired healing is associated with low levels of TGF‐β 1 . Histologic analysis confirmed previous demonstrations that exogenous TGF‐β 2 stimulates enhanced cellularity and connective tissue formation. Immunolocalization showed that exogenous TGF‐β 2 stimulates increased expression of endogenous TGF‐β 1 . Northern blot analysis revealed that TGF‐β 2 increased the expression of genes encoding the α 1 ‐chain of types I and III collagens and tissue inhibitor of metalloproteinase‐1. These observations show that TGF‐β 2 acts through a variety of mechanisms to stimulate repair in healing‐impaired wounds that are also deficient in endogenous TGF‐β 1 , but they do not distinguish between direct effects and indirect effects mediated by induced TGF‐β 1 .