Fibrosis in Preeclamptic Placentas Is Associated with Stromal Fibroblasts Activated by the Transforming Growth Factor-β1 Signaling Pathway

Takako Ohmaru-Nakanishi, Kazuo Asanoma, Mai Fujikawa, Yasuyuki Fujita, Hiroshi Yagi, Ichiro Onoyama, Nobuhiro Hidaka, Kenzo Sonoda, Kiyoko Kato

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Although fibrosis is one of the most prominent pathologic features of preeclamptic (PE) placentas, its mechanism remains largely unknown. Consistent with previous reports, we observed overexpression of collagen; actin, α2, smooth muscle, aorta; connective tissue growth factor; and fibronectin in PE placentas compared with control ones. To investigate the mechanism of fibrosis in PE placentas, placental fibroblasts were isolated from PE placentas or normal pregnancies at delivery. The expression of fibrosis-related factors in fibroblasts was evaluated by real-time RT-PCR, Western blotting, enzyme-linked immunosorbent assay, and gene microarrays. An in vitro collagen gel contraction assay was also performed. Fibroblasts isolated from PE placentas showed higher expression levels of fibrosis-related factors compared with those from control ones. Global gene expression profiling of PE fibroblasts was contrasted with that of control ones and indicated an intimate association with transforming growth factor-β1 (TGFB1) signaling. Furthermore, the PE fibroblasts expressed abundant phosphorylated SMAD family member 2 and showed higher expression levels of target genes of TGFB1 signaling compared with the control ones. The PE fibroblasts also had a greater ability to contract compared with the control ones. Contractility also depended on TGFB1 signaling. Our results suggest that TGFB1 signaling is activated in the fibroblasts in PE placentas and that these active fibroblasts contribute to fibrosis.

Original languageEnglish
Pages (from-to)683-695
Number of pages13
JournalAmerican Journal of Pathology
Volume188
Issue number3
DOIs
Publication statusPublished - Mar 2018

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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