HBO1 as an Important Target for the Treatment of CCL4-Induced Liver Fibrosis and Aged-Related Liver Aging and Fibrosis

Abstract

The liver is the largest digestive organ in the human body. The increasing incidence of chronic liver fibrosis is one of the major health challenges in the world. Liver fibrosis is a wound-healing response to acute or chronic cellular damage of liver tissue. At present, despite a series of research progress on the pathophysiological mechanism of fibrosis that has been made, there is still a gap in identifying antifibrotic targets and converting them into effective treatments. Therefore, it is extremely important to seek a molecular target that can alleviate or reverse liver fibrosis, which has important scientific and clinical significance. In the current study, to evaluate the therapeutic effect of HBO1 as a molecular target on liver aging and fibrosis, naturally-aged mice and CCL4-induced liver fibrosis mice were used as animal models, and multiple experiments were performed. Experimental results showed that HBO1 knockdown could strongly mitigate the accumulation of hepatic collagen by Masson and Sirius Red staining. Further study showed that HBO1 knockdown reduced the expression of fibrosis-related marker molecules (α-SMA, collagen type I (ColI), and fibronectin). Further work showed that HBO1 knockdown could significantly alleviate HSC activation. On this basis, we analyzed the underlying mechanism by which HBO1 alleviates liver fibrosis. It was found that HBO1 knockdown may modulate liver fibrosis by regulating the processes of EMT, inflammation, and oxidative stress. We further studied the effect of HBO1 knockdown on liver aging and aging-related liver fibrosis, and the results showed that HBO1 knockdown could significantly reduce the level of aging-related liver fibrosis and relieve liver aging. In conclusion, we systematically investigated the potential of HBO1 as a therapeutic target to attenuate liver fibrosis and liver aging. The current study found a crucial target for liver fibrosis and liver-aging therapy, which has laid a solid foundation for the liver fibrosis-related research.

Liver Fibrosis Amelioration by Macrophage-Biomimetic Polydopamine Nanoparticles via Synergistically Alleviating Inflammation and Scavenging ROS

“…This process is often accompanied by a vicious cycle involving inflammation and oxidative stress. − Multiple factors such as inflammatory cytokines, oxygen free radicals, or growth factors are believed to participate in the occurrence and development of liver fibrosis. ,− The accumulation of excess reactive oxygen species (ROS) during cell apoptosis or necrosis stimulates hepatic stellate cells (HSCs) to secrete pro-inflammatory mediators, thereby exacerbating inflammation and promoting the formation of scar tissue. ,− In turn, the secreted inflammatory mediators can further activate immune cells to release large amounts of ROS. Thus, excessive ROS and inflammation are mutually reinforcing through intercellular crosstalk. , However, most of the current therapeutic strategies have focused solely on managing either oxidative stress or inflammation. ,− For example, corticosteroids and ursodeoxycholic acid can suppress the release of pro-inflammatory cytokines . Antioxidants such as vitamin E, silymarin, and phosphatidylcholine may prevent HSC activation and protect hepatocytes from apoptosis .…”

Imaging misdiagnosis and clinical analysis of significant hepatic atrophy after bilioenteric anastomosis: A case report

“…The liver is the largest substantial digestive organ in the human body, involved in complex physiological functions, including digestion, metabolism, detoxification, excretion and so on[ 1 ]. The normal liver has a dual supply of blood and oxygen from the hepatic artery and portal vein, as well as biliary tract and nerve innervation in the hilum hepatis[ 2 , 3 ].…”