Etikala Anusha, Bruce Greg, Hudkins Kelly, Narayanan A S
Department of Pathology, Box 357470, University of Washington School of Medicine, Seattle, WA 98195-7470.
Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA 98101.
Biochem Biophys Rep. 2017 Jul;10:165-171. doi: 10.1016/j.bbrep.2017.03.012. Epub 2017 Apr 7.
LR8 gene was first reported in a subpopulation of cultured human lung fibroblasts expressing the receptor for C1q-globular domain, and it was not detectable in cultured endothelial cells and smooth muscle cells. LR8 mRNA levels were higher in fibrotic lungs. In this study we assessed LR8 production in human tissues and determined if the distribution of fibroblasts producing LR8 is affected in fibrosis. Normal and fibrotic tissue sections from human liver, lung and kidneys were immunostained with antibodies to LR8 and examined for the presence of fibroblasts staining positively and negatively. The cells were also examined for co-expression of α-smooth muscle actin (SMA), a marker for myofibroblasts. The results showed that LR8 was expressed by fibroblasts, smooth muscle cells, endothelial cells, bile duct cells, pulmonary alveolar cells and distal and proximal kidney tubule cells. Connective tissues of normal and fibrotic tissues contained fibroblasts staining positively and negatively with anti- LR8 antibody. The number of LR8-positive cells was higher in fibrotic tissues, but differences were not statistically significant. Fibroblasts producing both LR8 and SMA were present in higher numbers in fibrotic tissues as compared to normal tissues and the differences were statistically significant (p<0.05). Our results show that fibroblast subtypes differing in LR8 expression are present in human tissues, and that in fibrotic tissues cells co-expressing LR8 and SMA are present. Our results indicate that LR8 expressing cells may participate in the early stages of fibrotic diseases and that fibroblasts expressing LR8, not LR8 negative cells, have potential to become myofibroblasts in fibrotic tissues.
LR8基因最初是在一群表达C1q球状结构域受体的培养人肺成纤维细胞中被报道的,在培养的内皮细胞和平滑肌细胞中未检测到该基因。LR8 mRNA水平在纤维化肺组织中更高。在本研究中,我们评估了人组织中LR8的产生情况,并确定产生LR8的成纤维细胞分布在纤维化过程中是否受到影响。用人肝脏、肺和肾脏的正常和纤维化组织切片,用抗LR8抗体进行免疫染色,并检查阳性和阴性染色的成纤维细胞的存在情况。还检查了细胞中α-平滑肌肌动蛋白(SMA)的共表达情况,SMA是肌成纤维细胞的标志物。结果表明,LR8由成纤维细胞、平滑肌细胞、内皮细胞、胆管细胞、肺泡细胞以及远端和近端肾小管细胞表达。正常和纤维化组织的结缔组织中含有用抗LR8抗体染色呈阳性和阴性的成纤维细胞。LR8阳性细胞的数量在纤维化组织中更高,但差异无统计学意义。与正常组织相比,同时产生LR8和SMA的成纤维细胞在纤维化组织中的数量更多,差异具有统计学意义(p<0.05)。我们的结果表明,在人组织中存在LR8表达不同的成纤维细胞亚型,并且在纤维化组织中存在共表达LR8和SMA的细胞。我们的结果表明,表达LR8的细胞可能参与纤维化疾病的早期阶段,并且在纤维化组织中,表达LR8的成纤维细胞而非LR8阴性细胞有成为肌成纤维细胞的潜力。