Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22

Figure 1 Hepatic vagotomy inhibits liver regeneration and aggravates liver injury after partial hepatectomy. A: Representative BrdU staining pictures of liver tissue at different observation time points after partial hepatectomy (200 ×); B and C: The proportion of BrdU⁺ hepatocytes (48 h) and the liver weight/body weight ratio in each group were calculated to visually display the level of liver regeneration; D: Representative hematoxylin and eosin staining shows the area of liver injury after surgery (50 ×); E and F: Serum alanine aminotransferase and aspartate aminotransferase activities of mice in different groups were detected to determine the severity of liver injury (n = 6-10). ^aP < 0.05. PHx: Partial hepatectomy; Hv: Hepatic vagotomy; SP: Sham operation.

Figure 2 Hepatic vagotomy reduces interleukin-22 production after partial hepatectomy. A and B: A mouse interleukin (IL)-22 enzyme-linked immunosorbent assay kit was used to quantify the concentration of IL-22 in serum and liver homogenate of mice in each group; C-E: Liver tissues of different groups were obtained at 6 h after partial hepatectomy (PHx), and the expression of IL-22 protein (C and D) and IL-22 mRNA (E) in liver tissues were detected by western blotting and quantitative real-time polymerase chain reaction techniques, respectively (n = 6-10). ^aP < 0.05, ^bP < 0.01, ^cP < 0.001. PHx: Partial hepatectomy; Hv: Hepatic vagotomy; SP: Sham operation.

Figure 3 Hepatic vagotomy inhibits the activation of the hepatic signal transducer and activator of transcription 3 signaling pathway. A and B: Western blotting was used to detect the activation of the signal transducer and activator of transcription 3 pathway and the expression of its related proteins, such as CyclinD1, PCNA, and FoxM1, in liver tissues of each group at 6 h after partial hepatectomy. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001. PHx: Partial hepatectomy; Hv: Hepatic vagotomy; SP: Sham operation; STAT3: Signal transducer and activator of transcription 3.

Figure 4 Administration of exogenous interleukin-22 reverses the inhibition of liver regeneration caused by hepatic vagotomy. A: Representative BrdU staining pictures of liver tissues at 48 h from the partial hepatectomy (PHx)-hepatic vagotomy (Hv) group and the PHx-Hv-interleukin-22 group (200 ×); B and C: The proportion of BrdU⁺ hepatocytes (48 h) and the liver weight/body weight ratio of these two groups were counted; D and E: Serum alanine aminotransferase and aspartate aminotransferase activities of these two groups were detected to determine the severity of liver injury; F and G: Detection of the signal transducer and activator of transcription 3 pathway and related protein expression in mouse livers by western blotting (6 h) (n = 5-7). ^aP < 0.05. PHx: Partial hepatectomy; Hv: Hepatic vagotomy; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LW/BW: Liver weight/body weight; STAT3: Signal transducer and activator of transcription 3.

Figure 5 Treatment with interleukin-22BP can reduce the concentration of interleukin-22 and inhibit liver regeneration. A and B: The concentration of interleukin (IL)-22 in serum and liver tissue homogenate at each time point after partial hepatectomy (PHx) in the PHx-sham group and the PHx–IL-22BP group was counted; C: Representative BrdU staining pictures of liver tissue at different time points after PHx (200 ×); D: The percentage of BrdU⁺ hepatocytes (48 h) in the PHx-sham group and the PHx-IL-22BP group was calculated; E and F: We used an automatic chemical analyzer to detect the activities of serum alanine aminotransferase and aspartate aminotransferase in the PHx-sham group and the PHx–IL-22BP group (n = 4-8). ^aP < 0.05). PHx: Partial hepatectomy; Hv: Hepatic vagotomy; IL: Interleukin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Figure 6 Interleukin-22BP inhibits the activation of the hepatic signal transducer and activator of transcription 3 pathway after partial hepatectomy. The expression levels of signal transducer and activator of transcription 3 (STAT3), P-STAT3, and CyclinD1 protein in liver tissue of mice in the partial hepatectomy (PHx)-sham group and the PHx-interleukin-22BP group at 6 h after PHx were detected. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001. PHx: Partial hepatectomy; Hv: Hepatic vagotomy; STAT3: Signal transducer and activator of transcription 3; IL: Interleukin.