Whole transcriptome analysis of rat peritoneal cells in a TGFß1 induced mesothelial-to-mesenchymal transition

Peritoneal fibrosis is a major complication of long-term peritoneal dialysis (PD), leading to ultrafiltration failure and sometimes life threatening encapsulating peritoneal sclerosis. Fibrosis is driven by activated myofibroblasts that are derived, in part, from mesothelial-to-mesenchymal transition (MMT). We aimed to discover novel mediators of MMT and then experimentally exploit them to prevent peritoneal fibrosis. Using an antibody to HBME-1 and streptavidin nanobead technology, we first pioneered a novel method to purify rat mesothelial cells. After exposing mesothelial cells to transforming growth factor ß1 (TGFß1), we undertook RNAseq whole transcriptome analyses and outlined, the expression profile of sorted mesothelial cells at pre- and post- MMT.

腹膜纤维化是长期腹膜透析（PD）的主要并发症，可引发超滤衰竭，有时甚至会导致危及生命的包裹性腹膜硬化症。纤维化的驱动因素之一是活化肌成纤维细胞，这类细胞部分来源于间皮-间质转化（mesothelial-to-mesenchymal transition, MMT）。本研究旨在挖掘间皮-间质转化的新型调控介质，并通过实验手段验证其在预防腹膜纤维化中的作用。研究团队首先利用抗HBME-1抗体与链霉亲和素纳米磁珠技术，首创了一种纯化大鼠间皮细胞的全新方法。随后将间皮细胞暴露于转化生长因子β1（transforming growth factor β1, TGFβ1）中，开展全转录组RNAseq分析，明确了分选得到的间皮细胞在间皮-间质转化前后的基因表达谱特征。