Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice.
The highly ordered process of wound healing involves the coordinated regulation of cell proliferation and migration and tissue remodeling, predominantly by polypeptide growth factors. Consequently, the slowing of wound healing that occurs in the aged may be related to changes in the activity of these various regulatory factors. To gain additional insight into these issues, we quantified the absolute copy numbers of mRNAs encoding all the fibroblast growth factors (FGFs), their receptors (FGFRs) and two other growth factors in the dorsal skin of young and aged mice during the healing of full-thickness skin excisional wounds. In young adult mice (8 weeks old), FGF7, FGF10 and FGF22 mRNAs were all strongly expressed in healthy skin, and levels of FGF7 and 10 but not 22 increased 2- to 3.5-fold over differing time courses after wounding. The levels of FGF9, 16, 18 and especially 23 mRNAs were moderate or low in healthy skin but increased 2- to 33-fold after wounding. Among the four FGFRs, expression of only FGFR1 mRNA was augmented during wound healing. Expression of transforming growth factor-beta and hepatocyte growth factor was also high in healthy skin and was upregulated during healing. Notably, in aged mice (35 weeks old), where healing proceeded more slowly than in the young, both the basal and wound-induced mRNA expression of most of these genes was reduced. While these results confirm the established notion that FGFR2 IIIB ligands (FGF7 and FGF10) are important for wound healing, they also suggest that decreased expression of multiple FGF ligands contributes to the slowing of wound healing in aged mice and indicate the potential importance of further study of the involvement of FGF9, 16, 18 and 23 in the wound healing process.
Komi-Kuramochi
Akiko
A
Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Higashi, Tsukuba 305-8566, Ibaraki, Japan.
Kawano
Mitsuko
M
Oda
Yuko
Y
Asada
Masahiro
M
Suzuki
Masashi
M
Oki
Junko
J
Imamura
Toru
T
D000199:Actins / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000293:injuries* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014945:Wound Healing
D000199:Actins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases