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

Reproductive Diseases

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VOLUME 1, ISSUE 2, P206-220, NOVEMBER 01, 2020

Authors:

Minnie Malik, Ph.D., Joy Britten, M.D., Anthony DeAngelis, M.D., Ph.D., William H. Catherino, M.D., Ph.D. 

Abstract:

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.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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