Department of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Biochem Biophys Res Commun. 2021 Jul 5;561:180-186. doi: 10.1016/j.bbrc.2021.05.035. Epub 2021 May 21.
Fibrosis is a condition characterized by the overproduction of extracellular matrix (ECM) components (e.g., collagen) in the myofibroblasts, causing tissue hardening and eventual organ dysfunction. Currently, the molecular mechanisms that regulate ECM production in the myofibroblasts are still obscure. In this study, we investigated the function of GPRC5B in the cardiac and lung myofibroblasts using real-time RT-PCR and siRNA-mediated knockdown. We discovered a significantly high expression of Gprc5b in the tissues of the fibrosis mice models and confirmed that Gprc5b was consistently expressed in the myofibroblasts of fibrotic hearts and lungs. We also found that Gprc5b expression was associated and may be dependent on the actin-MRTF-SRF signaling pathway. Notably, we observed that Gprc5b knockdown reduced the expression of collagen genes in the cardiac and lung myofibroblasts. Therefore, our findings reveal that GPRC5B enhances collagen production in the myofibroblasts, which directly promotes fibrosis in the tissues.
纤维化是一种特征为肌成纤维细胞中细胞外基质（ECM）成分（如胶原）过度产生的疾病，导致组织硬化和最终的器官功能障碍。目前，调节肌成纤维细胞中 ECM 产生的分子机制仍不清楚。在这项研究中，我们使用实时 RT-PCR 和 siRNA 介导的敲低研究了 GPRC5B 在心脏和肺肌成纤维细胞中的功能。我们发现纤维化小鼠模型组织中 Gprc5b 的表达明显升高，并证实 Gprc5b 在纤维化心脏和肺部的肌成纤维细胞中持续表达。我们还发现 Gprc5b 的表达与肌动蛋白-MRTF-SRF 信号通路有关，并且可能依赖于该信号通路。值得注意的是，我们观察到 Gprc5b 敲低减少了心脏和肺肌成纤维细胞中胶原基因的表达。因此，我们的研究结果表明，GPRC5B 增强了肌成纤维细胞中胶原的产生，从而直接促进了组织中的纤维化。
