BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA prog...BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.展开更多
基金National Natural Science Foundation of China,No.82372194.
文摘BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.
