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. 2026 Jan 23;83(1):79. doi: 10.1007/s00018-025-06040-w

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© The Author(s) 2026

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 5 — BMP6 is elevated in patients with PE and in PE model rats. A-C, BMP6 is elevated in patients with PE. A, RT‒qPCR analysis of BMP6 mRNA expression levels in the placentas of control women (n = 10) and PE patients (n = 10), with GAPDH as the reference gene. B, Western blot analysis of BMP6 protein expression levels in the placentas of control women (n = 4) and PE patients (n = 4). C, Spearman correlation analysis between the placental BMP6 mRNA levels and the value of log10 (SBP) of the corresponding patients. The gray area represents the 95% CI. Each dot represents one sample. D, The animal experimental protocol. E and F, BMP6 is elevated in the plasma of PE model rats. Rat plasma levels of BMP6 (E) and PlGF (F) in the Ad Fc + PBS group (n = 4) and Ad Flt1 + PBS group (n = 4). G-M, BMP6 is elevated in the placenta of PE model rats at G13. RNA-seq analysis of rat placentas at G13 in the Ad Fc + PBS group (n = 3) and Ad Flt1 + PBS group (n = 3). G, Heatmap depicting DEGs in the two groups. H, Dot plots of significantly enriched GO terms; the dot size represents the number of DEGs associated with a particular GO term. I, KEGG hierarchical network plot of pathways. J, GSEA-KEGG Ridge plot of pathways. K, GSEA plots of cytokine-cytokine receptor interaction pathway. L, Volcano plot of RNA-seq data showing DEGs between the Ad Fc + PBS group and the Ad Flt1 + PBS group. M, Circos graph displaying the coexpression networks of five genes in rat placenta samples. Each sector of the circle represents one gene, and its width indicates the total amount of co-occurrence that connects one gene to the other. The width of each link represents the total number of coexpressed genes among the linked genes. Student’s t-test was used for comparisons between two groups in A, B, E, and F. Groups without common letters are significantly different from each other (P < 0.05). SD, Sprague–Dawley; BMP6, bone morphogenetic protein 6; PlGF, placental growth factor; PBS, phosphate-buffered saline; Ad Flt1, adenovirus expressing fms-like tyrosine kinase-1; Ad Fc, adenovirus-expressing control IgG2a Fc fragment; FC, fold change; Serpine2, serpin family E member 2; Id1, inhibitor of DNA-binding 1