الفهرس 
Epidemiology of liver fibrosis
Inflammatory signaling and leukocyte chemoattractionOnly 14 pages are availabe for public view
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Abstract
Hepatic fibrosis is a result of the wound-healing response of the liver to repeated injury. This process is associated with an inflammatory response and a limited deposition of extracellular matrix (ECM). Fibrosis occurs when ECM proteins accumulate in excessive amounts, leading to scarring that distorts the normal layout and stiffness of the tissue (Cordero-Espinoza and Huch., 2018).
Hepatic fibrosis was historically thought to be a passive process due to the collapse of the hepatic parenchyma and its substitution with collagen-rich tissue (Kim et al., 2017). Currently, it is considered a model of the wound-healing response to chronic liver injury (Shen et al., 2017). Therefore, researchers have been stimulated to identify antifibrotic therapies.
WNT/β-catenin is an evolutionarily conserved cellular signaling system that plays an essential role in diverse arrays of biologic processes such as organogenesis, tissue homeostasis, and pathogenesis of many human diseases. Activated Wnt/β-catenin signaling has been implicated in fibrosis in many organs, including lung, kidney, skin, and liver (Nishikawa et al., 2018). So, modulation of WNT pathway may present as a suitable and promising therapeutic strategy through the inhibitions of its key points as Frizzled protein (FZD), Dishevelled protein (Dvl), β-catenin destruction complex, nuclear β-catenin and porcupine (Prcn) enzyme (Tran and Zheng, 2017).
Glutamine, the most abundant intracellular free amino acid, has many important functions. It can be converted to α-ketoglutarate and enters tricarboxylic acid cycle (TCA) cycle as energy fuel or
Chapter I Introduction and Aim of the Work
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converted to other amino acids including proline. Previous studies show that glutamate may serve as a major anaplerotic precursor in the proliferating fibroblast, which suggested an increased glutaminolysis that meets the energy need for collagen synthesis (Li et al., 2017). Therefore, any disruption of glutaminolysis pathway has enormous effect on cell proliferation and collagen production (Li et al., 2017).
Niclosamide is an oral antihelminthic drug used to treat parasitic infections in millions of people worldwide. Niclosamide may have broad clinical applications for the treatment of diseases other than those caused by parasites (Chen et al., 2018). Niclosamide can inhibit the Wnt signaling pathway by downregulating Dvl expression, resulting in decreased downstream β-catenin signaling (Tran et al., 2017).
Lithium is used for the treatment of some psychological disorder such as bipolar disorder (BD), acute manic, mixed and depressive episodes of BD (Won and Kim, 2017). Lithium is also considered a Wnt activator as it works by inhibiting the glycogen synthase kinase-3β (GSK-3β) enzyme found in the β-catenin destruction complex. By inhibiting this enzyme, β-catenin is accumulated in the nucleus allowing Wnt signaling transcription (Tran et al., 2017).