1. Academic Validation
  2. Autocrine Production of Interleukin-34 Promotes the Development of Endometriosis through CSF1R/JAK3/STAT6 signaling

Autocrine Production of Interleukin-34 Promotes the Development of Endometriosis through CSF1R/JAK3/STAT6 signaling

  • Sci Rep. 2019 Nov 14;9(1):16781. doi: 10.1038/s41598-019-52741-1.
Kaiqing Lin 1 Junyan Ma 2 Yaomin Peng 2 Meina Sun 1 Kaihong Xu 1 Ruijin Wu 1 Jun Lin 3
Affiliations

Affiliations

  • 1 Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, People's Republic of China.
  • 2 Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, 310006, Hangzhou, People's Republic of China.
  • 3 Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, People's Republic of China. [email protected].
Abstract

Interleukin (IL)-34 plays a critical role in cell proliferation, differentiation, Apoptosis, angiogenesis, inflammation and immunoregulation. Numerous diseases can be attributed to the dysregulation of IL-34 signaling. This study was performed to investigate the function of IL-34 in the pathogenesis of endometriosis. Firstly, by Enzyme linked immunoabsorbent assay, we found that IL-34, VEGF, MMP-2 and MMP-9 were increased in the sera of patients with endometriosis. Secondly, exposure to IL-34 promoted the proliferation, migration and invasion of eutopic endometrial stromal cells (ESCs). Additionally, stimulation with IL-34 up-regulated colony-stimulating factor 1 receptor (CSF1R), p-JAK3, p-STAT6, VEGF, MMP-2 and MMP-9 in these eutopic ESCs. Treatment with AS1517499, an inhibitor of STAT6, remarkably abrogated the alterations induced by IL-34. A Chromatin immunoprecipitation (ChIP) assay demonstrated binding of STAT6 to the IL-34 promoter, further implicating STAT6 in IL-34 signaling. Notably, reverse results were obtained in ectopic ESCs with the application of an IL-34 neutralizing antibody. In vivo, AS1517499 suppressed the maintenance of endometriosis lesions in rats. In summary, autocrine production of IL-34, mediated by STAT6, promoted the development of endometriosis in vitro and in vivo through the CSF1R/JAK3/STAT6 pathway. Our research reveals the function of IL-34 in endometriosis, which may provide insight into novel therapeutic strategies for endometriosis.

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