Department of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Disease Control, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan.
Biochem Biophys Res Commun. 2024 Nov 19;734:150785. doi: 10.1016/j.bbrc.2024.150785. Epub 2024 Oct 2.
Fibrosis results from the excessive production of extracellular matrix proteins by myofibroblasts. It has recently been reported that in the heart, myofibroblasts develop chondrocyte-like properties following myocardial infarction as fibrosis progresses and tissues stiffen. However, the nature of these chondrocyte-like myofibroblasts remains unclear. In this study, we found that the expression of the proline- and arginine-rich end leucine-rich repeat protein (PRELP) was upregulated in hearts and livers stiffened by fibrosis with chronic inflammation. Moreover, we established that Prelp was specifically expressed in chondrocyte-like myofibroblasts. Prelp expression was found to be regulated by the transcription factor SOX9, and in cardiac and liver myofibroblasts, Prelp-knockdown was observed to reduce collagen expression. These findings reveal that PRELP is specifically expressed in chondrocyte-like myofibroblasts and that it promotes collagen production. PRELP could thus serve as a novel therapeutic target for treating fibrosis.
纤维化是由肌成纤维细胞过度产生细胞外基质蛋白引起的。最近有报道称，在心肌梗死后，随着纤维化的进展和组织变硬，心肌中的肌成纤维细胞会发展出类似软骨细胞的特性。然而，这些类似软骨细胞的肌成纤维细胞的性质尚不清楚。在这项研究中，我们发现，在纤维化导致的心脏和肝脏僵硬的慢性炎症中，脯氨酸和精氨酸丰富的末端亮氨酸丰富重复蛋白（PRELP）的表达上调。此外，我们确定 Prelp 特异性表达在类似软骨细胞的肌成纤维细胞中。发现 Prelp 的表达受转录因子 SOX9 调控，在心脏和肝脏肌成纤维细胞中，观察到 Prelp 敲低可减少胶原蛋白的表达。这些发现表明 PRELP 特异性表达在类似软骨细胞的肌成纤维细胞中，并促进胶原蛋白的产生。因此，PRELP 可以作为治疗纤维化的新的治疗靶点。
