Ratcliffe Don R, Iqbal Jahangir, Hussain M Mahmood, Cramer Eva B
Department of Anatomy, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
Biochim Biophys Acta. 2009 Dec;1791(12):1144-54. doi: 10.1016/j.bbalip.2009.07.005. Epub 2009 Jul 29.
Caco-2 cells spontaneously differentiate into enterocyte-like cells and secrete apolipoprotein B (apoB) lipoproteins. We evaluated the effect of different extracellular matrix proteins on lipoprotein secretion by these cells. Caco-2 cells grown on human amnion connective tissue (HACT) secreted twice as much apoB as control cells on Transwells, but secreted similar amounts of apoA1. Cells cultured on fibrillar collagen type I secreted increased amounts of apoB similar to the cells cultured on HACT, but cells cultured on non-fibrillar collagen type I, type IV collagen or laminin-1 did not. The increased secretion was nullified by a function inhibiting anti-integrin beta1 monoclonal antibody. Therefore, interactions between type I collagen and beta1 integrins augment apoB secretion by Caco-2 cells. Cells on HACT formed a more uniform columnar epithelium with lipid droplets polarized to the basolateral membrane. We also studied the effect of extracellular matrix proteins on transepithelial resistance (TER) of differentiated Caco-2 cells. TER in cells cultured on HACT was similar to that on Transwells, but cells on laminin-1 and collagen IV exhibited higher TER. Thus, various extracellular matrix proteins regulate apoB secretion and TER differently. This new observation that extracellular matrix proteins can enhance apoB secretion in Caco-2 cells could be useful to explore the modulation of lipid transport by these proteins.
Caco-2细胞可自发分化为肠上皮样细胞并分泌载脂蛋白B（apoB）脂蛋白。我们评估了不同细胞外基质蛋白对这些细胞脂蛋白分泌的影响。在人羊膜结缔组织（HACT）上生长的Caco-2细胞分泌的apoB是Transwell上对照细胞的两倍，但apoA1的分泌量相似。在I型纤维状胶原蛋白上培养的细胞分泌的apoB量增加，与在HACT上培养的细胞相似，但在I型非纤维状胶原蛋白、IV型胶原蛋白或层粘连蛋白-1上培养的细胞则不然。一种功能抑制性抗整合素β1单克隆抗体可消除这种分泌增加的现象。因此，I型胶原蛋白与β1整合素之间的相互作用增强了Caco-2细胞的apoB分泌。HACT上的细胞形成了更均匀的柱状上皮，脂滴极化至基底外侧膜。我们还研究了细胞外基质蛋白对分化的Caco-2细胞跨上皮电阻（TER）的影响。在HACT上培养的细胞的TER与在Transwell上培养的细胞相似，但在层粘连蛋白-1和IV型胶原蛋白上的细胞表现出更高的TER。因此，各种细胞外基质蛋白对apoB分泌和TER的调节方式不同。细胞外基质蛋白可增强Caco-2细胞中apoB分泌这一新发现，可能有助于探索这些蛋白对脂质转运的调节作用。
