Knock-down of IGFBP2 ameliorates lung fibrosis and inflammation in rats with severe pneumonia through STAT3 pathway

Objective: To observe the mechanism of IGFBP2 knock-down in improving lung fibrosis and inflammation through STAT3 pathway in rats with severe pneumonia. Materials and Methods: First, SP rat model was established. Then rats were divided into the Control group, the SP group, the SPthornLv-vector shRNA group, the SPthornLv-IGFBP2 shRNA group, the SPthornLv-vector group, and the SPthornLv-IGFBP2 group. The mRNA and protein levels of IGFBP2, NOS, CD206 and Arg 1 were detected by RT-qPCR and Western blot. IHC was used to check the positive expression of IGFBP2 and MCP1. A fully automated blood gas analyzer was used to detected PaCO2, CO2 content, PaO2 and SaO2. HE and Masson staining were performed to observe the lung tissue injury and collagen deposition of rats in each group. ELISA assays were used to calculate the levels of inflammatory factors IL-1 beta, IL-6, TNF-alpha, IL-4, and IL-10. Flow cytometry was conducted to acquire the ratio of M1-type AMs and M2-type AMs. Results: Compared with the Control group, IGFBP2, iNOS, CD206, and Arg1 mRNA and protein expression levels, IGFBP2 and MCP1 positive expressions, PaCO2, p-STAT3/STAT3, p-JAK2/JAK2, IL-1 beta, IL-6, and TNF-alpha levels, the number of AMs and neutrophils, the proportion of M1 type AMs and the expressions of alpha-SMA, Collagen-I, Collagen III, and Fibronectin were significantly increased in SP rats (p < 0.05), while PaCO2, CO2, and SaO(2), IL-4 and IL-10 levels, and the proportion of M2 type AMs decreased (p< 0.05). However, the knockdown of IGFBP2 reversed the above index trends. Conclusion: Knock-down of IGFBP2 ameliorated lung injury in SP rats, inhibited inflammation and pulmonary fibrosis, and promoted M2-type transformation of AMs by activating the STAT3 pathway.

Automated summary

Knockdown of IGFBP2 improves lung fibrosis and inflammation in rats with severe pneumonia by promoting M2-type transformation of alveolar macrophages (AMs) through the STAT3 pathway.