On Nicholas, Koh Sabrina P, Brasch Helen D, Dunne Jonathan C, Armstrong James R, Tan Swee T, Itinteang Tinte
Gillies McIndoe Research Institute; and Wellington Regional Plastic, Reconstructive, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand.
Plast Reconstr Surg Glob Open. 2017 Jul 24;5(7):e1422. doi: 10.1097/GOX.0000000000001422. eCollection 2017 Jul.
The renin-angiotensin system (RAS) mediates cardiac and renal fibrosis. Dupuytren's disease (DD) is a proliferative fibromatosis affecting the hands. This study investigated the expression of the RAS in DD.
3,3-Diaminobenzidine (DAB) and immunofluorescent immunohistochemical (IHC) staining for (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (ATIIR2) was performed on 4-μm thick formalin-fixed paraffin-embedded sections of DD cords and nodules from 6 patients. Western blotting (WB) and NanoString mRNA analysis were performed to confirm RAS protein expression and transcriptional activation, respectively.
IHC staining demonstrated the expression of PRR, ACE, ATIIR1, and ATIIR2 on the ERG and CD34 endothelium of the micro vessels surrounding the DD cords and nodules. PRR was also expressed on the pericyte layer of these microvessels. WB confirmed protein expression of PRR, ACE, and ATIIR2 but not ATIIR1. NanoString analysis confirmed transcriptional activation of PRR, ACE, ATIIR1, but ATIIR2 was below detectable levels.
We demonstrated expression of PRR, ATIIR1, ATIIR2, and ACE on the embryonic stem cell-like cell population on the microvessels surrounding DD nodules and cords by IHC staining, although the expression of ATIIR1 was not confirmed by WB and that of ATIIR2 was below detectable levels on NanoString analysis. These findings suggest the embryonic stem cell-like cell population as a potential therapeutic target for DD, by using RAS modulators.
肾素-血管紧张素系统（RAS）介导心脏和肾脏纤维化。杜普伊特伦挛缩病（DD）是一种影响手部的增生性纤维瘤病。本研究调查了RAS在DD中的表达。
对6例患者的DD条索和结节的4μm厚福尔马林固定石蜡包埋切片进行3,3-二氨基联苯胺（DAB）和免疫荧光免疫组织化学（IHC）染色，检测（前）肾素受体（PRR）、血管紧张素转换酶（ACE）、血管紧张素II受体1（ATIIR1）和血管紧张素II受体2（ATIIR2）。分别进行蛋白质印迹法（WB）和NanoString mRNA分析以确认RAS蛋白表达和转录激活。
免疫组织化学染色显示PRR、ACE、ATIIR1和ATIIR2在DD条索和结节周围微血管的ERG和CD34内皮细胞上表达。PRR也在这些微血管的周细胞层表达。蛋白质印迹法证实了PRR、ACE和ATIIR2的蛋白表达，但未证实ATIIR1的表达。NanoString分析证实了PRR、ACE、ATIIR1的转录激活，但ATIIR2低于可检测水平。
我们通过免疫组织化学染色证明了PRR、ATIIR1、ATIIR2和ACE在DD结节和条索周围微血管上的胚胎干细胞样细胞群体中的表达，尽管蛋白质印迹法未证实ATIIR1的表达，且NanoString分析显示ATIIR2低于可检测水平。这些发现表明，通过使用RAS调节剂，胚胎干细胞样细胞群体可能是DD的潜在治疗靶点。
