Matrix Biology ( IF 6.9 ) Pub Date : 2022-04-19 , DOI: 10.1016/j.matbio.2022.04.004 Matthias Przyklenk 1 , Veronika S Georgieva 2 , Fabian Metzen 1 , Sebastian Mostert 1 , Birgit Kobbe 1 , Bert Callewaert 3 , Gerhard Sengle 4 , Bent Brachvogel 2 , Robert P Mecham 5 , Mats Paulsson 6 , Raimund Wagener 6 , Manuel Koch 7 , Alvise Schiavinato 8
LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillin-microfibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and -2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.
中文翻译:
LTBP1促进原纤维蛋白掺入细胞外基质
LTBP1 是一种大的细胞外基质蛋白和原纤维蛋白-微纤维的相关配体。对 LTBP1 功能的了解在很大程度上仅限于其在细胞外基质内靶向和隔离 TGFβ 生长因子中的作用,从而调节它们的生物利用度。然而,最近对携带 LTBP1 致病性变异的患者的多种组织中的广泛表型的描述表明,该蛋白质在结缔组织的稳态中具有多方面的作用。为了更好地了解由 LTBP1 缺乏引起的人类病理学,研究其在细胞外基质形成中的功能作用非常重要。在这项研究中,我们表明 LTBP1在体外协调 fibrillin-1 和 -2 掺入细胞外基质中. 我们还证明了这种功能是由两种亚型(LTBP1 的短形式和长形式)不同地发挥的。因此,我们的研究结果揭示了一种新的不依赖 TGFβ 的 LTBP1 功能,可能有助于结缔组织疾病的发展。