Modulation of extracellular matrix proteins in rat liver during development

Abstract

The expression and localization of extracellular matrix proteins in rat liver was investigated as a function of liver development. Levels of extracellular matrix proteins were measured by dot-blot or immunoblot protocols using monospecific antibodies prepared against collagen types I, III and IV; laminin; fibronectin; and fibronectin receptor. Proline and hydroxyproline levels from extracted liver collagen were quantitated by Pico Tag analysis. It was observed that the content of type IV collagen and fibronectin in the rat liver increased two to four times during the perinatal period. In contrast, levels of laminin and collagen types I and III decreased up to twofold in developing rat livers. The content of fibronectin receptor during ontogeny was decreased four times in an inverse relationship to fibronectin molecules. Fibronectin receptor and extracellular matrix proteins displayed no difference in apparent molecular weight as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots. Indirect immunofluorescence staining of frozen thin liver sections revealed that the pattern of localization of extracellular matrix proteins in the nonvascular regions of fetal liver was punctate rather than restricted to a specific region such as the perisinusoidal area of adult livers. Similarly, fibronectin receptor was also present, mainly in the sinusoidal area of adult livers, whereas fetal sections were diffusely stained. Our findings suggest that the differential modulation of extracellular matrix proteins and their localization in the developing rat livers undergo a dramatic alteration in the composition and structural organization of matrix material, which may act to modulate proliferation and to promote the differentiation of liver cells during development.

Histological changes in the liver of fetuses of alcohol-treated pregnant rats

“…3 The cellular sources of individual ECM proteins in liver have been reported to be derived from hepatocytes, lipocytes and sinusoidal cells. 4 As is well known, the liver is particularly affected by alcohol toxicity; important changes may occur in liver histology and its ECM with alcohol treatment.…”

“…5 Type IV collagen, found in hepatic sinusoids, promotes hepatocyte proliferation, 6 but it inhibits the further proliferation of the liver cells in the postnatal period. 4 TN and type IV collagen have an important role in liver development and growth, and tissue damage. Therefore, these ECM components were selected for study.…”

Distribution of Collagen I, III, and IV and Laminin in the Human Liver during Prenatal Development

“…During liver development, collagen IV and laminin were present in the hepatic PSP in the form of discontinuous deposits. The proportion of collagen IV increases with gestational age and equals that of laminin during the early postnatal period [Reif et al, 1990;Elkasaby et al, 1991;Baloch et al, 1992;Amenta and Harrison, 1993;Ober and Lemaigre, 2018]. Studies of rat fetal livers showed that in early stages of hepatogenesis and in the postnatal regenerating liver, the sinusoids were covered with a continuous endothelium but without morphologically recognizable BM, despite the presence of collagen IV and laminin in the PSP [Amenta and Harrison, 1997;Shiojiri and Sugiyama, 2004;Zeisberg et al, 2006;Kuo et al, 2012;Mak et al, 2013;Zhou et al, 2016].…”

“…The main ECM components are collagens I, III, and IV. In addition, matrix glycoproteins, fibronectin, laminin, and heparan sulfate proteoglycan are present in considerable amounts [Hirata et al, 1983;Reif et al, 1990;Elkasaby et al, 1991;Martinez-Hernandez and Amenta, 1993a;Gersdorff et al, 2005;Shoulders and Raines, 2009;Mao et al, 2015]. Collagens I, III, and IV and laminin provides an environment that favors the extension of nerves and blood and lymph vessels within the organ [Amenta and Harrison, 1997;Kim et al, 1997;Tiniakos et al, 2008;Mak et al, 2012].…”

Obesity and Air Pollution: Global Risk Factors for Pediatric Non-alcoholic Fatty Liver Disease

“…Of special concern in the context of this epidemic is the escalating trend in the prevalence of childhood overweight and obesity on a global scale. There are several reports on the increasing prevalence of childhood obesity in industrialized countries [9][10][11][12][13][14]; however, this is an emerging health problem in low- and middle-income countries as well [15][16][17][18]. An analysis of 450 nationally representative crosssectional surveys of preschool-aged children from 144 countries indicated that in 2010, 43 million children, 35 million of them in developing countries, were estimated to be overweight and obese, and 92 million were at risk of becoming overweight.…”