Transcription Factor KLF4 Mediates the Transformation of Scar-Associated Macrophages Driven by Plasminogen from Bone Marrow-Derived Monocytes/Macrophages
YANG Lin, YANG Yuanru, LI liying, CHANG Na*
SAM (scar-associated macrophage) plays an important role in liver fibrogenesis. PLG (plasminogen) drives the transformation of macrophage to SAM, but the underlying mechanism is still unclear. The aim of this study is to explore the mechanism underlying PLG-driven SAM transformation. scRNA-seq (single-cell RNA sequencing) data were analyzed. The results showed that transcriptional factor KLF4 (Krüppel-like factor 4) was highly expressed by SAM. Isolated mouse primary BMDMs (bone marrow-derived monocyte/macrophages) were treated with PLG to induce SAM transformation. Specific siRNA was used to knock down KLF4 expression in BMDMs. The protein expression of genes was studied using flow cytometry and Western blot. Immunofluorescence was employed to study the localization of KLF4. RT-qPCR was used to detect the mRNA expression of genes. The results showed that PLG triggered the up-regulation and nuclear localization of KLF4. The knockdown of KLF4 expression blocked PLG-driven SAM transformation. The expressions of SAM feature/functional genes, the ratio of SAM, and the ability to induce extracellular matrix prodection by hepatic stellate cells were decreased. The overexpression of KLF4 increased SAM feature/functional gene expressions. In conclusion, KLF4 plays an important role in PLG-driven SAM transformation.
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