Feige J J, Keramidas M, Chambaz E M
INSERM Unité 244, Département de Biologie Moléculaire et Structurale, CEA Grenoble, France.
Horm Metab Res. 1998 Jun-Jul;30(6-7):421-5. doi: 10.1055/s-2007-978908.
The extracellular matrix (ECM) strongly contributes to the regulation of cell proliferation and cell differentiation, and thereby of embryonic development and adult tissue homeostasis. We review here the ongoing characterization of the structure and functions of the extracellular matrix components secreted by adrenocortical cells and discuss their possible implication in the hormonal regulation of adrenal cortex homeostasis. Fibronectin (FN) and laminin (LN) are both major adhesive proteins for adrenocortical cells. FN is synthesized by bovine fasciculata cells in primary culture, and its synthesis is stimulated by TGF(beta)1, TGF(beta)2, and FGF-2 but is not modified by IGF-1 or by the hormones ACTH and angiotensin II. LN is also synthesized by bovine fasciculata cells and its synthesis is specifically stimulated by ACTH. Both proteins are haptotactic and chemotactic for adrenocortical cells, suggesting a physiological role in adrenocyte migration. Their distribution in the adrenal gland is quite distinct. LN is uniformly present in the steroidogenic cells from the three zones, whereas FN is abundant in the fibrovascular structures of the capsule and the cortex. ACTH treatment of adrenocortical cells strongly induces the expression and secretion of thrombospondin-2 (TSP2), a large trimeric matricellular protein. The multimodular structure of TSP2 is the support of a variety of biological functions. TSP2 promotes attachment but prevents spreading of adrenocortical cells. On the other hand, TSP2 induces the activation of latent TGFbeta through an indirect mechanism and is anti-angiogenic in vitro. The overall distribution of TSP2 in the glomerulosa and fasciculata zones of the adrenal cortex, and its absence from the reticularis zone, argue in favor of a role in the protection of adrenocortical cells against apoptosis. In the adrenal cortex, five main biological functions are potentially regulated by components of the extracellular matrix : stem cell commitment into the adrenocyte differentiation pathway, terminal differentiation toward the three distinct adrenocyte phenotypes, centripetal migration, apoptosis and the formation of the capillary network. Future studies will aim at deciphering which extracellular component(s) is involved in each of these regulations.
细胞外基质（ECM）对细胞增殖和细胞分化的调节起着重要作用，进而影响胚胎发育和成年组织的稳态。在此，我们综述了肾上腺皮质细胞分泌的细胞外基质成分的结构和功能的研究进展，并讨论了它们在肾上腺皮质稳态激素调节中的可能作用。纤连蛋白（FN）和层粘连蛋白（LN）都是肾上腺皮质细胞的主要黏附蛋白。FN由原代培养的牛束状带细胞合成，其合成受转化生长因子β1（TGF-β1）、转化生长因子β2（TGF-β2）和碱性成纤维细胞生长因子-2（FGF-2）刺激，但不受胰岛素样生长因子-1（IGF-1）、促肾上腺皮质激素（ACTH）和血管紧张素II的影响。LN也由牛束状带细胞合成，其合成受ACTH特异性刺激。这两种蛋白对肾上腺皮质细胞都具有趋触性和趋化性，表明它们在肾上腺细胞迁移中具有生理作用。它们在肾上腺中的分布截然不同。LN均匀存在于三个带的类固醇生成细胞中，而FN在被膜和皮质的纤维血管结构中丰富。ACTH处理肾上腺皮质细胞可强烈诱导血小板反应蛋白-2（TSP2）的表达和分泌，TSP2是一种大型三聚体基质细胞蛋白。TSP2的多模块结构支持多种生物学功能。TSP2促进肾上腺皮质细胞黏附但阻止其铺展。另一方面，TSP2通过间接机制诱导潜伏性TGF-β的激活，并且在体外具有抗血管生成作用。TSP2在肾上腺皮质球状带和束状带的总体分布以及在网状带的缺失，表明其在保护肾上腺皮质细胞免受凋亡方面发挥作用。在肾上腺皮质中，细胞外基质的成分可能调节五种主要生物学功能：干细胞向肾上腺细胞分化途径的定向分化、向三种不同肾上腺细胞表型的终末分化、向心性迁移、凋亡以及毛细血管网络的形成。未来的研究旨在阐明每种调节中涉及哪些细胞外成分。
