Differential regulation of fibulin, tenascin-C, and nidogen expression during wound healing of normal and glucocorticoid-treated mice.
Expression and distribution of fibulins, nidogen, and tenascin-C were analyzed in healing skin wounds of normal and dexamethasone-treated mice. In normal mice both tenascin-C and fibulin-2 showed a marked increase in mRNA expression, which declined to normal levels after completion of skin repair. These two matrix proteins are found throughout the granulation tissue and persisted there after mRNA expression had ceased. Fibulin-1 is present in normal skin and in wounds but is not distinctly upregulated during the healing process. Nidogen, however, is expressed uniformly throughout the granulation tissue early in wound healing, has a peak expression around Day 7, and selectively localizes to basement membranes after healing is accomplished. Dexamethasone treatment led to a decreased expression of tenascin-C in healing wounds but had no effect on fibulin-2 expression. In vitro experiments revealed that growth factors like TGF-beta 1 can partly counteract glucocorticoid action. These data therefore provide some molecular interpretations for the well-known glucocorticoid suppression of wound healing. They also indicate that repair involves complex regulatory processes which are obviously different for each of the four proteins studied.
Fässler
R
R
Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany.
Sasaki
T
T
Timpl
R
R
Chu
M L
ML
Werner
S
S
D016475:3T3 Cells; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004817:Epidermis / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D019063:Tenascin / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019063:Tenascin; D016212:Transforming Growth Factor beta; C060820:fibulin; C084612:fibulin 2; C029967:nidogen; D003907:Dexamethasone