Xia Y P, Zhao Y, Marcus J, Jimenez P A, Ruben S M, Moore P A, Khan F, Mustoe T A
Department of Surgery, Northwestern University, Chicago, IL 60611, USA.
J Pathol. 1999 Aug;188(4):431-8. doi: 10.1002/(SICI)1096-9896(199908)188:4<431::AID-PATH362>3.0.CO;2-B.
Keratinocyte growth factor-2 (KGF-2), also described as fibroblast growth factor-10 (FGF-10), is a member of the fibroblast growth factor family. KGF-2 shares 57 per cent sequence homology to previously reported KGF-1 (FGF-7). In skin, both growth factors are expressed in the dermal compartment. KGF-1 and KGF-2 bind to the same receptor with high affinity, the KGFR isoform of FGFR2, which is exclusively expressed by epithelial cells. This study examines the in vivo function of topically applied KGF-2 on wound healing using an ischaemia-impaired rabbit dermal ulcer model, in young and aged animals. Histological analysis of the wounds showed that KGF-2 significantly promoted re-epithelialization in both young and old animals. Similar results have been observed with KGF-1 in this model. In addition, KGF-2 enhanced granulation tissue formation in both young and old rabbits, a biological effect not found with KGF-1, suggesting a possible indirect mechanism which enhances neo-granulation tissue formation. Immunohistological staining of day 7 wounds with proliferating cell nuclear antigen (PCNA) antibody demonstrated a significant increase of dermal cell proliferation in KGF-2-treated wounds compared with placebo wounds. These results suggest a mesenchymal-epithelial interaction that is mediated by a paracrine feedback loop of KGF-2. Because of the wound healing impairment observed with ageing, the wound healing response to KGF-2 was also studied in ischaemic wounds of aged animals. Administration of KGF-2 led to significant stimulation of epithelial growth and granulation tissue formation. The effects seen in the old animals were delayed compared with the young animals. Lastly, the effect of KGF-2 was examined in a rabbit model of scar formation. Quantification of scar elevation index showed no significant differences in scar formation when KGF-2 was compared with buffer placebo. Compared with other growth factors, including KGF-1 and TGF-beta which have previously been examined in these models, KGF-2 is the most effective and causes no obvious scarring.
角质形成细胞生长因子-2（KGF-2），也被称为成纤维细胞生长因子-10（FGF-10），是成纤维细胞生长因子家族的一员。KGF-2与先前报道的KGF-1（FGF-7）有57%的序列同源性。在皮肤中，这两种生长因子都在真皮层表达。KGF-1和KGF-2以高亲和力结合同一受体，即FGFR2的KGFR亚型，该亚型仅由上皮细胞表达。本研究使用缺血损伤的兔真皮溃疡模型，在年轻和老年动物中研究局部应用KGF-2对伤口愈合的体内功能。伤口的组织学分析表明，KGF-2在年轻和老年动物中均显著促进了上皮再形成。在该模型中，KGF-1也观察到了类似结果。此外，KGF-2增强了年轻和老年兔子的肉芽组织形成，这是KGF-1未发现的生物学效应，提示可能存在一种间接机制来增强新肉芽组织形成。用增殖细胞核抗原（PCNA）抗体对第7天的伤口进行免疫组织化学染色显示，与安慰剂处理的伤口相比，KGF-2处理的伤口中真皮细胞增殖显著增加。这些结果提示了一种由KGF-2的旁分泌反馈环介导的间充质-上皮相互作用。由于观察到衰老会导致伤口愈合受损，因此也在老年动物的缺血伤口中研究了对KGF-2的伤口愈合反应。给予KGF-2可显著刺激上皮生长和肉芽组织形成。与年轻动物相比，老年动物中观察到的效应出现延迟。最后，在兔瘢痕形成模型中研究了KGF-2的作用。瘢痕隆起指数定量显示，与缓冲液安慰剂相比，KGF-2处理时瘢痕形成无显著差异。与先前在这些模型中研究过的其他生长因子（包括KGF-1和TGF-β）相比，KGF-2最有效且不会导致明显瘢痕形成。
