Equipe de Recherche sur les Relations Matrice Extracellulaire Cellules, ERRMECe (EA 1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Maison International de la Recherche, CY Cergy Paris Université, 1 rue Descartes, 95000, Neuville-sur-Oise, France.
Laboratoires Clarins, 5 rue Ampère, 95300, Pontoise, France.
Exp Cell Res. 2024 Oct 1;442(2):114251. doi: 10.1016/j.yexcr.2024.114251. Epub 2024 Sep 10.
Fibronectin (Fn) is a ubiquitous extracellular matrix (ECM) glycoprotein that acts as an ECM scaffold organizer and is essential in many biological functions, including tissue repair, differentiation or cancer dissemination. Evidence suggests that the amount of Fn changes during aging. However, how these changes influence the aging process remains unclear. This study aims to understand Fn influence on cell aging. First, we assess the relative level of Fn abundance in both different biopsies of skin donors and replicative senescence cellular model. In skin biopsies, we observed that Fn level decreases with aging in the reticular dermis, while its expression remains relatively stable in the papillary dermis, likely to sustain the dermis-epidermis junction. During replicative senescence, in BJ skin fibroblasts, while intracellular Fn increases, we found that secretion and Fn fibrils formation are less effective. Reduced Fn fibrils leads to disorganization of the ECM. This could be explained by the expression of different Fn isoforms observed in the secretome of senescent cells. Surprisingly, the knockdown of Fn delays the onset of senescence while cultivating cells onto a Fn-coated support promotes it. Taken together, these new insights on the role of Fn during aging may emerge new therapeutic strategies on aged-related diseases.
纤连蛋白（Fn）是一种普遍存在的细胞外基质（ECM）糖蛋白，作为 ECM 支架组织者，在许多生物学功能中至关重要，包括组织修复、分化或癌症扩散。有证据表明，Fn 的含量会随着衰老而变化。然而，这些变化如何影响衰老过程尚不清楚。本研究旨在了解 Fn 对细胞衰老的影响。首先，我们评估了皮肤供体的不同活检样本和复制性衰老细胞模型中 Fn 丰度的相对水平。在皮肤活检中，我们观察到随着真皮网状层的衰老，Fn 水平降低，而其在真皮乳头层的表达相对稳定，可能维持真皮-表皮交界处。在复制性衰老过程中，BJ 皮肤成纤维细胞中，虽然细胞内 Fn 增加，但我们发现分泌和 Fn 纤维形成的效果较差。减少的 Fn 纤维导致 ECM 组织紊乱。这可以通过在衰老细胞的分泌组中观察到的不同 Fn 异构体的表达来解释。令人惊讶的是，Fn 的敲低延迟了细胞衰老的发生，而在 Fn 涂层支持物上培养细胞则促进了衰老的发生。总之，这些关于 Fn 在衰老过程中作用的新见解可能会为与年龄相关的疾病出现新的治疗策略。
