CES1 is associated with alleviating keloid fibrotic characteristics potentially by modulating JAK/STAT‑mediated M2‑like macrophage polarization in in vitro models

Keloids are characterized by excessive fibrosis driven by interactions between fibroblasts and macrophages.Carboxylesterase 1 (CES1) is associated with fibrosis, but its role in keloid pathogenesis remains unclear.The present study aimed to explore the role of CES1 in keloid fibrosis and its regulation of macrophage-fibroblast interactions.Differential expression analysis was performed on keloid datasets (GSE92566, GSE121618 and GSE158766).KEL FIB cells and M0 macrophages or M2 macrophages were co-cultured.Cellular interactions were evaluated using the Cell Counting Kit-8 assay to assess proliferation, while flow cytometry was used to assess apoptosis.Additionally, fibrosis-related markers (collagen III, collagen I, TGF-β, vimentin, α-smooth muscle actin and fibronectin), M2 macrophage polarization markers (CD206 and CD163) and components of the JAK/STAT signaling pathway were assessed using western blotting, immunofluorescence and reverse transcription-quantitative PCR.Bioinformatics analysis showed that CES1 expression was downregulated in keloid tissues compared with normal skin tissues.Co-culture with M0 macrophages enhanced KEL FIB cell proliferation and reduced apoptosis while upregulating fibrotic markers.Conversely, KEL FIB cells induced M2-like polarization of M0 macrophages, as characterized by the increased expression of CD163 and CD206.CES1 overexpression in KEL FIB cells was associated with reduced phosphorylated STAT5 levels, suggesting a potential modulatory effect on the JAK/STAT signaling pathway, accompanied by decreased expression of fibrotic markers in KEL FIB cells and M2 polarization markers in co-cultured M0 macrophages.CES1 knockdown resulted in the opposite effects, which was mitigated by the STAT5 inhibitor AC-4-130.However, CES1 overexpression did not notably alter fibrotic markers in KEL FIB cells co-cultured with M2 macrophages.The results of the present study suggested a key role for CES1 in modulating keloid fibrosis, possibly by modulating M2 polarization through the JAK/STAT signaling pathway in vitro.Targeting CES1 and macrophage-fibroblast interactions may provide a novel research direction and a promising therapeutic strategy for keloid treatment.