Large induction of keratinocyte growth factor expression in the dermis during wound healing.

Abstract

Recent studies have shown that appliaton of basic fibroblast growth factor (basic FGF) to a wound has a beneficial effect. However, it has not been whether endogenous FGF also plays a role in tissue repair. In this study we found a 160-fold induction of mRNA encoding keratinocyte growth factor (KGF) 1 day after skin injury. This large induction was unique within the family of FGFs, since mRNA lvel of acidic FGF, basc FGF, and FGF-5 were only slightly induced (2-to 10-fold) during wound healing, and there was no expression of FGF-3, FGF-4, and FGF-6 deed in normal and wounded skin. gh levels of FGF receptor 1 and FGF receptor 2 mRNA and iow levels ofFGF receptor 3 mRNA were found in both normal and wounded skin. No change in the levels of these transcripts was detected during wound healing. In situ hybridization studies revealed highest levels of KGF mRNA expression in the dermis at the wound edge and in the hypodermis beiow the wound. In contrast, mRNA encoding the receptor of this growth factor (a splice variant of FGF receptor 2) was predominantly expressed in the epidermis. These results suggest that basal keratinocytes are stimulated by dermally derived KGF during wound healing and implte a unique role of this member of the FGF family in wound repair.

Neu differentiation factor/heregulin induction by hepatocyte and keratinocyte growth factors

“…A band of the expected size was detected 1 day after injury, and the level of induction continued to increase to a maximum at 5 days (Figure 7). This pattern was consistent with the temporal pro®le of KGF induction at wound sites documented previously using this animal model (Werner et al, 1992), suggesting that the NDF induction we observed was the result of locally increased KGF activity.…”

“…The induction of NDF was detected in a mouse model of skin wound healing where KGF has been shown to be strongly upregulated within 24 h after injury (Werner et al, 1992). We also observed signi®cant NDF induction in the kidneys of partially hepatectomized mice, where circulating HGF levels are increased in response to liver failure (Kinoshita et al, 1991;Lindroos et al, 1991).…”

“…Results are representative of two experiments with identical ®ndings these growth factors have been reported to be elevated. KGF is potently induced in cutaneous wounds within 24 h after injury (Werner et al, 1992). We determined the relative levels of NDF expression in a mouse model of cutaneous wound repair by RNase protection assay using a riboprobe at the 3' end UTR of NDF ( Figure 7).…”

Dehydrated human amnion/chorion membrane regulates stem cell activity in vitro

“…These growth cytokines are known to stimulate cell proliferation, migration, differentiation, cell survival, and protein synthesis, and have been shown to enhance healing of wounds 42, 43, 44, 45. Additionally, TIMP‐1, which was also upregulated, is an inhibitor of MMPs and is actively involved in tissue remodeling processes 46…”

A Novel Enhancer of the Wound Healing Process

“…11 Several types of FGFs are expressed at the wound site, including FGF1, FGF2, FGF7, FGF10, and FGF22, and the expression of some of them is greatly increased at different phases of the repair process. 12,13 This is functionally important because FGF2 knockout mice have impaired wound healing, 14 and expression of a dominant-negative FGFR2 mutant in keratinocytes of transgenic mice resulted in a severe delay in wound re-epithelialization. 15 Therefore, FGF signaling is obviously required for efficient healing.…”