Dupuis Loren E, Kern Christine B
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
Dev Dyn. 2014 Apr;243(4):601-11. doi: 10.1002/dvdy.24100. Epub 2014 Jan 4.
Small Leucine Rich Proteoglycans (SLRPs) play a role in collagen fiber formation and also function as signaling molecules. Given the importance of collagen synthesis to the cardiovascular extracellular matrix (ECM), we examined the spatiotemporal expression of SLRPs, not previously investigated in the murine heart.
Cardiac expression using antibodies specific for biglycan (BGN), decorin (DCN), fibromodulin (FMOD), and lumican (LUM) revealed distinct patterns among the SLRPs in mesenchymal-derived tissues. DCN showed the most intense localization within the developing valve cusps, while LUM was evident primarily in the hinge region of postnatal cardiac valves. BGN, DCN, and FMOD were immunolocalized to regions where cardiac valves anchor into adjacent tissues. Medial (BGN) and adventitial (BGN, DCN, FMOD and LUM) layers of the pulmonary and aortic arteries also showed intense staining of SLRPs but this spatiotemporal expression varied with developmental age.
The unique expression patterns of SLRPs suggest they have adapted to specialized roles in the cardiovascular ECM. SLRP expression patterns overlap with areas where TGFβ signaling is critical to the developing heart. Therefore, we speculate that SLRPs may not only be required to facilitate collagen fiber formation but may also regulate TGFβ signaling in the murine heart.
富含亮氨酸的小分子蛋白聚糖(SLRPs)在胶原纤维形成中发挥作用,并且还作为信号分子起作用。鉴于胶原合成对心血管细胞外基质(ECM)的重要性,我们研究了SLRPs的时空表达,此前尚未在小鼠心脏中进行过此项研究。
使用针对双糖链蛋白聚糖(BGN)、核心蛋白聚糖(DCN)、纤维调节蛋白(FMOD)和光蛋白聚糖(LUM)的特异性抗体进行心脏表达研究,结果显示间充质来源组织中的SLRPs呈现出不同的模式。DCN在发育中的瓣膜尖内显示出最强烈的定位,而LUM主要在出生后心脏瓣膜的铰链区域明显可见。BGN、DCN和FMOD免疫定位到心脏瓣膜锚定到相邻组织的区域。肺动脉和主动脉的中层(BGN)和外膜层(BGN、DCN、FMOD和LUM)也显示出SLRPs的强烈染色,但这种时空表达随发育年龄而变化。
SLRPs独特的表达模式表明它们已适应在心血管ECM中发挥特殊作用。SLRP表达模式与TGFβ信号传导对发育中心脏至关重要的区域重叠。因此,我们推测SLRPs可能不仅是促进胶原纤维形成所必需的,而且可能在小鼠心脏中调节TGFβ信号传导。