Expression of intracellular adhesion molecule 1 by activated hepatic stellate cells

Abstract

The hepatic stellate cell (HSC), following a fibrogenic stimThe hepatic stellate cell (HSC), following a fibrogenic ulus, undergoes an activation process in which changes occur stimulus, is transformed from a quiescent to an actiin cellular morphology, cellular metabolism, and in the patvated cell. HSC activation results in numerous changes tern of gene expression. These changes include morphological in cellular morphology, cellular metabolism, and in the changes to a myofibroblast-like cell with the appearance of pattern of gene expression. Many of the changes that are smooth muscle a-actin, a loss in cellular retinol stores, and an observed in activated HSCs in animal models of hepatic increase in the rough endoplasmic reticulum. [1][2][3][4][5] In addition, fibrosis are also seen when these cells are activated by activation of HSCs in vivo results in the induction of plateletculturing on plastic. These changes include morphologiderived growth factor b receptors, 6 transforming growth faccal changes to a myofibroblast-like cell with the appeartor b, 7-9 and multiple extracellular matrix proteins, including ance of smooth muscle a-actin, a loss of the retinol proteoglycans and type I collagen. 1,3,[10][11][12] Metabolic changes stores, an increase in the rough endoplasmic reticulum, include an increase in DNA synthesis and in cellular proliferand increases in extracellular matrix production, ination. cluding a dramatic increase in type I collagen. To idenMany of the morphological and metabolic changes associtify additional genes that are induced or suppressed durated with HSC activation in animal models of fibrosis also ing HSC activation, we used the differential polymerase occur when these cells are grown in culture on plastic. In chain reaction (PCR) display technique. Using this techculture, HSCs show alterations in cellular morphology, innique, we isolated a complementary DNA (cDNA) frag-cluding an increase in the appearance of rough endoplasmic ment for the intercellular adhesion molecule 1 (ICAM-1). reticulum, a loss of the retinol stores, and an increase in Northern blotting confirmed that the ICAM-1 messenger the proliferation rate.13,14 Cultured HSCs also initiate the RNA (mRNA) was expressed in HSCs activated by cul-synthesis of smooth muscle a-actin, and the expression of ture, but not in quiescent, freshly isolated HSCs. The new receptors, including the platelet-derived growth factor presence of ICAM-1 protein was demonstrated in cul-b receptor 6 and transforming growth factor b receptors I and ture-activated HSCs, but not in quiescent cells by West-II. 15 The expression of several extracellular matrix proteins ern blot analysis and immunohistochemical staining. A is increased, including several proteoglycans 16 and type I colfunctional assay was performed, demonstrating that lagen synthesis at both the messenger RNA (mRNA) and lymphocytes will adhere to activated HSCs and that protein levels. 13,14,[17][18][19][20][21][22][23][24][25] treatment of these cells with tumor necrosis factor a Differen...

Impact of rapamycin on liver regeneration

“…It seems likely that posttranscriptional factors might be involved in downregulation of α-SMA or collagen after RAPA treatment. Down-regulation of ICAM-1 mRNA expression in liver after RAPA treatment was observed here first suggesting that transmigration of leucocytes in sinusoids during inflammation might be also affected [10,16].…”

Viral and bacterial patterns induce TLR-mediated sustained inflammation and calcification in aortic valve interstitial cells

“…Since poly (I:C) is known to induce adhesion molecules expression [24], it is important to mention that cell cultures were free from endothelial contaminants that could account for ICAM-1 expression (data not shown). Furthermore, ICAM-1 might play an important role on myofibroblast function, since it has been described to be expressed in myofibroblast-like cells like such as hepatic stellate cells [25]. Interestingly, in a recent multi-ethnic study of atherosclerosis, soluble ICAM-1 was associated with increased prevalence and severity of aortic valve calcification [26].…”

Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis

“…The percent of BM engraftment was evaluated in mice transplanted with b-actin-GFP by FACS analysis of peripheral blood lymphocytes (PBL) and constituted 95%. Using BMT, we generated 51 Col-into-wt mice, 7 Wt-into-Col mice, 3 wt-into-wt and 3 Col-into-Col. Liver injury was induced for 14-28 days by ligation of the common bile duct (BDL) as described [20]. All animal studies have been approved by the University Committee on Use and Care of Animals at Columbia University.…”