Mouse Models of Liver Fibrosis Mimic Human Liver Fibrosis of Different Etiologies

Abstract

The liver has the amazing capacity to repair itself after injury; however, the same processes that are involved in liver regeneration after acute injury can cause serious consequences during chronic liver injury. In an effort to repair damage, activated hepatic stellate cells trigger a cascade of events that lead to deposition and accumulation of extracellular matrix components causing the progressive replacement of the liver parenchyma by scar tissue, thus resulting in fibrosis. Although fibrosis occurs as a result of many chronic liver diseases, the molecular mechanisms involved depend on the underlying etiology. Since studying liver fibrosis in human subjects is complicated by many factors, mouse models of liver fibrosis that mimic the human conditions fill this void. This review summarizes the general mouse models of liver fibrosis and mouse models that mimic specific human disease conditions that result in liver fibrosis. Additionally, recent progress that has been made in understanding the molecular mechanisms involved in the fibrogenic processes of each of the human disease conditions is highlighted.

Role of hemostatic factors in hepatic injury and disease: animal models de‐liver

“…For example, hepatic fibrosis develops in rodents after chronic exposure to xenobiotics, including carbon tetrachloride (CCl 4 ), thioacetamide, α‐naphthylisothiocyanate (ANIT), 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine, dimethyl‐nitrosamine, or diethyl‐nitrosamine. The basis for each of these models has been reviewed elsewhere . Hepatic fibrosis (i.e.…”

“…This leads to hepatic parenchymal cell damage by multiple mechanisms, including disruption of intracellular calcium homeostasis and lipid peroxidation . The lesion produced by acute CCl 4 administration is typified by necrosis of centrilobular hepatocytes, which undergo wound healing to restore the normal hepatic architecture . Persistent hepatocellular injury elicited by chronic CCl 4 administration to rodents, typically every 3–4 days, for several weeks, results in bridging hepatic fibrosis.…”

“…Persistent hepatocellular injury elicited by chronic CCl 4 administration to rodents, typically every 3–4 days, for several weeks, results in bridging hepatic fibrosis. Very prolonged exposure, particularly in rats, produces cirrhosis and even hepatocellular carcinoma . This model has been extensively utilized to decipher the fundamental mechanisms of hepatic stellate cell activation and hepatic fibrosis.…”

Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon Tetrachloride–Induced Model of Liver Injury

“…Because of its anti-inflammatory effect, celecoxib has been explored as a possible therapy in several models of liver fibrosis, such as the thioacetamide (TAA)-and carbon tetrachloride (CCl 4 )-induced rodent models and the surgical bile duct ligation (BDL) rodent model. CCl 4 acts primarily through an increase in hepatic lipid peroxidation and oxidative stress, whereas TAA acts primarily through an increase in oxidative stress, processes that damage hepatocytes and trigger fibrosis (Martínez et al, 2014). BDL is a surgical model in which the bile duct is partially ligated, leading to cholestasis, liver ABBREVIATIONS: APAP, acetaminophen; BDL, bile duct ligation; CCl 4 , carbon tetrachloride; COX, cyclooxygenase; EET, epoxyeicosatrienoic acid; HSC, hepatic stellate cell; IHC, immunohistochemistry; LC-MS/MS, liquid chromatography-tandem mass spectrometry; LOX, lipoxygenase; LXA 4 , lipoxin A4; MMP, matrix metalloprotease; NSAID, nonsteroidal anti-inflammatory drug; P450, cytochrome P450; PGD 2 , prostaglandin D2; PGE 2 , prostaglandin E2; PGJ 2 , prostaglandin J2; PTUPB, 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl)-benzenesulfonamide; sEH, soluble epoxide hydrolase; sEHI, soluble epoxide hydrolase inhibitor; SMA, smooth muscle actin; TAA, thioacetamide; TIMP, tissue inhibitor of metalloproteases; TGF, transforming growth factor; TPPU, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea.…”

“…damage, and fibrosis (Martínez et al, 2014). In some models, treatment with celecoxib has resulted in a reduction in fibrosis and inflammation, whereas in others, including some rat CCl 4 -induced models, celecoxib has worsened liver damage and fibrosis (Hui et al, 2006;Paik et al, 2009;Chávez et al, 2010).…”