Cross-talk between Janus kinase-signal transducer and activator of transcription pathway and transforming growth factor beta pathways and increased collagen1A1 production in uterine leiomyoma cells

Objective: To characterize the potential interaction between interleukin-6 (IL6), Janus kinase (JAK)-signal transducer and activator of transcription (STAT)-3 (JAK/STAT3) pathway, and Transforming growth factor beta (TGFβ)-3, and to determine whether such cross-talk was a contributing factor in the dysregulation of type I collagen production in leiomyomas. Design: Laboratory study. Setting: University research laboratory. Patients: None. Interventions: Exposure of leiomyoma and myometrial cell lines to IL6 and STAT3 activators/inhibitors. Western immunoblot analysis and immunohistochemistry. Main Outcome Measures: Expression of STAT3, pSTAT3, SOCS3, COL1A1, and TGFb3. Results: We observed that IL6 increased pSTAT3 as well as collagen1A1 in uterine leiomyoma cells. Direct activation of the JAK/STAT3 pathway increased collagen1A1 production in leiomyoma cells, whereas inhibition of the pathway significantly decreased collagen1A1 production. We further observed that modulation of the JAK/STAT3 pathway also increased the expression of TGFβ3 protein. Leiomyoma cells exposed to TGFβ3 demonstrated a significant decrease in pSTAT3 protein. Myometrial cells demonstrated a less sensitive response to STAT3 modulation and collagen production. Conclusion: Cross-talk between the TGFβ pathway and JAK/STAT3 pathway contributes to the fibrotic nature of uterine leiomyomas.