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

Abstract

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 5 th 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.

Exploring the role of growth factors as potential regulators in psoriatic plaque formation

“…HGF is a cytokine that has been shown to exert anti‐inflammatory effects in various tissues, 75–79 including the skin 80,81 and oral mucosa 82 . We previously reported that the HGF activation z‐score was higher at the plaque centre than at the periphery, which could potentially lead to central regression of the plaques 9 .…”

“…Evidence shows that HGF inhibits p56 NF‐κB binding to the target gene promoter, suppressing NF‐κB activity, and also inhibits NF‐κB‐dependent secretion of IL‐6 induced by IL‐1β and TNF‐α in human renal epithelial cells 76 . HGF has been shown to improve oral ulcer by attenuating neutrophil infiltration in the ulcer area and suppressing proinflammatory cytokines in a mouse model 82 . Interestingly, in a psoriasis model, HGF‐overexpressing dental pulp stem cells showed an anti‐inflammatory effect with improvement of psoriatic mice skin via suppression of Th1 and Th17 and upregulation of T regs, with reduction of IFN‐γ, TNF‐α and IL‐17A and upregulation of IL‐10 80 .…”

“…76 HGF has been shown to improve oral ulcer by attenuating neutrophil infiltration in the ulcer area and suppressing proinflammatory cytokines in a mouse model. 82 Interestingly, in a psoriasis model, HGF-overexpressing dental pulp stem cells showed an anti-inflammatory effect with improvement of psoriatic mice skin via suppression of Th1 and Th17 and upregulation of T regs, with reduction of IFNγ, TNFα and IL-17A and upregulation of IL-10. 80 Despite evidence showing that HGF has anti-inflammatory effects, our results indicate that its functions as GF regulator that is associated with upregulation of downstream genes involved in inflammation (AHR, CXCL8, NAMPT and LCN2) and proliferation (ITGB1 and MKI67).…”