Anti-inflammatory effect of HGF responses to oral traumatic ulcers using an HGF-Tg mouse model

Hepatocyte growth factor (HGF) has been implicated in inhibiting diverse types of inflammation. Oral traumatic ulceration (OTU) is a common disease of the oral mucosa, and inflammation is the main process for ulcer healing. This study aimed to explore the expression of HGF in oral ulcers and its role in ulcer inflammation. The saliva of 14 recurrent alphous stomatitis (RAS) patients, 18 OTU patients and 17 healthy controls was collected. Traumatic ulcers of the left mucosa were observed in 42 wild-type (WT) and 42 HGF-overexpressing transgenic (HGF-Tg) mice. Histological scores, inflammatory cell expression and serum cytokine expression were measured and analyzed on the 5th day. The HGF protein level in ulcer-affected human saliva was 9.3-fold higher than that in healthy saliva. The HGF protein levels in RAS and OTU saliva were 14- and 5.7-fold higher, respectively, than those in healthy saliva. Traumatic ulcers enhanced HGF expression in ulcer-affected oral mucosa and in the blood of C57BL/6 mice by 1.21- and 1.40-fold, respectively. In HGF-Tg mouse traumatic ulcers, HGF expression was 1.34-fold higher than that in wild-type mice. HGF-Tg mice had lower weight loss, less ulcer area and lower histopathology scores than WT mice. The results from immunohistochemistry, flow cytometry and serum cytokine analysis showed that HGF-Tg animals presented fewer Ly6G-positive neutrophils and higher levels of circulating inflammatory cytokines. HGF overexpression alleviated weight loss, ulcer area and inflammation, suggesting the role of HGF in promoting the healing of oral ulcers.