This rat model reproduces the key features of human NASH and provides a realistic experimental model for elucidating its treatment.

Basement membranes provide structural support to epithelium, endothelium, muscles, fat cells, Schwann cells, and axons. Basement membranes are multifunctional: they modulate cellular behavior, regulate organogenesis, promote tissue repair, form a barrier to filtration and tumor metastasis, bind growth factors, and mediate angiogenesis. All basement membranes contain type IV collagen (Col IV), laminin, nidogen, and perlecan. Col IV and laminin self-assemble into two independent supramolecular networks that are linked to nidogen and perlecan to form a morphological discernable basement membrane/basal lamina. The triple helical region, 7S domain and NCI domain of Col IV, laminin and laminin fragment P1 have been evaluated as noninvasive fibrosis biomarkers of alcoholic liver disease, viral hepatitis, and nonalcoholic fatty liver disease. Elevated serum Col IV and laminin are related to degrees of fibrosis and severity of hepatitis, and may reflect hepatic basement membrane metabolism. But the serum assays have not been linked to disclosing the anatomical sites and lobular distribution of perisinusoidal basement membrane formation in the liver. Hepatic sinusoids normally lack a basement membrane, although Col IV is a normal matrix component of the space of Disse. In liver disease, laminin deposits in the space of Disse and codistributes with Col IV, forming a perisinusoidal basement membrane. Concomitantly, the sinusoidal endothelium loses its fenestrae and is transformed into vascular type endothelium. These changes lead to capillarization of hepatic sinusoids, a significant pathology that impairs hepatic function. Accordingly, codistribution of Col IV and laminin serves as histochemical marker of perisinusoidal basement membrane formation in liver disease. Anat Rec, 300:1371-1390, 2017. © 2017 Wiley Periodicals, Inc.

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Type V collagen (COLV) is a regulatory fibril-forming collagen. It has at least three different molecular isoforms-a1(V) 2 a2(V), a1(V) 3, and a1(V)a2(V)a3(V)-formed by combinations of three different polypeptide a chains-a1(V), a2(V), and a3(V). COL V is a relatively minor collagen of the extracellular matrix (ECM). Morphologically, COLV occurs as heterotypic fibrils with type I collagen (COLI), microfilaments, or 12-nm-thick fibrils. COLV is synthesized in various mesenchymal cells and its gene expression is modulated by TGF-b and growth factors. While resistant to digestion by interstitial collagenases, native and denatured COLV are degraded by metalloproteinases and gelatinases, thereby promoting ECM remodeling. COLV interacts with matrix collagens and structural proteins, conferring structural integrity to tissue scaffolds. It binds matrix macromolecules, modulating cellular behavior, and functions. COLV coassembles with COLI into heterotypic fibrils in the cornea and skin dermis, acting as a dominant regulator of collagen fibrillogenesis. COLV deficiency is associated with loss of corneal transparency and classic EhlersDanlos syndrome, while COLV overexpression is found in cancer, granulation tissue, inflammation, atherosclerosis, and fibrosis of lungs, skin, kidneys, adipose tissue, and liver. COLV isoform containing the a3(V) chain is involved in mediating pancreatic islet cell functions. In the liver, COLV is a minor but regular component of the ECM. Increases in COLV are associated with both early and advanced hepatic fibrosis. The neoepitopes of COLV have been shown to be a useful noninvasive serum biomarker for assessing fibrotic progression and resolution in experimental hepatic fibrosis. COLV is multifunctional in health, disease, and fibrosis. Anat Rec, 299:613-629, 2016. V C 2016 Wiley Periodicals, Inc.Key words: collagen V synthesis and degradation; collagen V deficiency and overexpression; collagen V in disease and fibrosis; collagen V neoepitopes; hepatic fibrosis biomarker

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Lipocytes and transitional cells in alcoholic liver disease were analyzed by quantitative morphometry in liver biopsy specimens of 17 alcoholic patients. In fatty livers, 93% of the perisinusoidal cells were lipocytes with a volume of lipid droplets occupying more than 20% of the individual cell volume. In fatty livers with perivenular fibrosis, 83% of the cells were lipocytes and 17% were transitional cells with lipid droplets of less than 20% of the cell volume. In cirrhosis, 45% of the cells were lipocytes and 55% of the cells were transitional cells. Thus, the process of hepatic fibrosis was associated with a shift from lipocytes to transitional cells. The percentage of transitional cells (expressed as total perisinusoidal cells) was 5.1% in fatty livers, 16.5% in fatty livers with perivenular fibrosis (not significantly different when compared to fatty livers) and 59.7% in cirrhotic livers (p less than 0.025) when compared to fatty livers or fatty livers with perivenular fibrosis). The number of transitional cells per 100 hepatocytes was estimated to be 0.5 in fatty livers, 1.3 in fatty livers with perivenular fibrosis and 2.1 in cirrhotic livers. The appearance of transitional cells was associated with a corresponding decrease in the number of lipocytes, supporting the hypothesis that transitional cells were derived from lipocytes. In comparison to lipocytes, the surface area of transitional cells (as measured by digitized morphometry) was 30 to 46% smaller (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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