The liver, gallbladder and pancreas
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Within the parenchyma of the liver there is a complex network of cells. Although the predominant cell type is the hepatocyte, a significant number of other cells, both resident and transitory, are important. Hepatocytes are arranged in plates, lining the blood-filled sinusoids. Sinusoidal endothelial cells are fenestrated, allowing direct access of hepatocytes to constituents of the blood. On the sinusoidal endothelial wall lie phagocytic Kupffer cells and within the perisinusoidal space of Disse are the hepatic stellate cells; these are myofibroblast precursors important in liver fibrosis (Figure 11.3). Liver-specific natural killer (NK) cells are located within the space of Disse and play an important role in the innate immune system response to viral infections. When liver cells are injured, regeneration is rapid and may be complete. Proliferation of hepatocytes can occur anywhere in the acinus, although experimental studies suggest that there is a reserve of hepatic progenitor cells close to the portal tract, within the canal of Hering, the ductular compartment connecting the bile canaliculi to the bile ductules at the limiting plate. The hepatic progenitor cells are capable of differentiating into hepatocytes and/or bile duct cells (cholangiocytes) when toxic injury or extensive hepatic necrosis precludes regeneration of mature hepatocytes.
Structure and function of the mesothelial cell
Wim P. Ceelen, Edward A. Levine in Intraperitoneal Cancer Therapy, 2015
Lipopolysaccharide (LPS), a derivative of bacterial cell wall, has also been found to induce MMT and is proposed to be a possible mechanism whereby peritonitis is linked to peritoneal fibrosis [36]. In vivo, a number of studies have reported the importance of mesothelial cells in the development of fibrosis following injury. We have shown, using a rat peritoneal scrape injury model, that DiI-labeled rat mesothelial cells injected into the peritoneal cavity are incorporated into the mesothelial layer, eventually appearing in the subserosa [37]. Furthermore, adenovirus-mediated overexpression of TGF-β1 in the lung and peritoneum induced fibrosis in mice that was associated with MMT and reduced epithelial cell (E-cadherin) and increased myofibroblast (collagen type 1, α-SMA, matrix metalloproteinase [MMP]-2 and MMP-9) marker expression [38,39]. Li et al. [14], using conditional cell lineage murine studies, also demonstrated that hepatic stellate cells and myofibroblasts are derived from mesothelial cells expressing WT1 that had undergone MMT during liver fibrogenesis. In a study using similar techniques, WT1-positive pleural mesothelial cells migrated into the lung parenchyma leading to idiopathic lung fibrosis following TGF-β1 treatment in mice [40].
Advances in Nanonutraceuticals: Indian Scenario
Harishkumar Madhyastha, Durgesh Nandini Chauhan in Nanopharmaceuticals in Regenerative Medicine, 2022
Persistent inflammation, following liver damage, often results in the formation of fibrous tissue. Therefore, often, any medication which is given to reduce the inflammation ideally has an anti-fibrotic effect. The sequence of steps, which lead to fibrosis are outlined as oxidative stress caused by the generation of ROS followed by scar formation, leading to a reduced inflammatory response. This inflammation causes the crippling of hepatic stellate cell (HSC) activation causing fibrogenesis as seen in cirrhosis of the liver. In this context, it can be said, that certain natural compounds or Unani preparations which are identified as antioxidants, can be given as a therapy to reduce the ROS and in a way to prevent fibrosis of hepatic tissue. The effectiveness of this treatment depends upon the agility of the antioxidant reaching the target site i.e., liver (Kawada et al. 1998).
Nonalcoholic steatohepatitis (NASH) cirrhosis: a snapshot of therapeutic agents in clinical development and the optimal design for clinical trials
Published in Expert Opinion on Investigational Drugs, 2022
Pankaj Aggarwal, Mazen Noureddin, Stephen Harrison, Sophie Jeannin, Naim Alkhouri
We envision a future where patients with NASH cirrhosis can be accurately identified without the need for invasive liver biopsy based on NITs. The same NITs will be used as surrogate efficacy endpoints that predict the future development of MALO. Establishing the threshold for change in NITs that corresponds with clinical outcomes is urgently needed before further implementation. We anticipate that the next 5 years will witness a revolution in the way we manage our patients with cirrhotic NASH. New methods to more accurately measure portal pressure are being developed including endoscopic ultrasound and spleen stiffness. New discoveries on the roles of different subsets of hepatic stellate cells in disease progression are likely to translate into relevant therapeutic interventions. Furthermore, RNA interference through antisense oligonucleotides and short interfering RNAs is a novel method to alter the expression of several genetic variants that play significant roles in the development and progression of NAFLD such as DGAT2, PNPLA3, and HSD17β13. The promise of precision medicine is finally becoming a reality as these highly selective therapeutics are being developed at a rapid pace.
Circulating liver-specific microRNAs as noninvasive diagnostic biomarkers of hepatic diseases in human
Published in Biomarkers, 2019
Ghulam Musaddaq, Naveed Shahzad, Muhammad Adnan Ashraf, Muhammad Imran Arshad
Liver fibrosis is the excessive accumulation of extracellular matrix produced by hepatic stellate cells (HSCs) following continuous inflammatory process. Liver biopsy is still the reference procedure to assess liver fibrosis and cirrhosis (Saleh and Abu-Rashed 2007). Currently, miRNAs have been shown to play a role in the activation of HSC and proliferation thus regulating the progression of liver fibrosis. The miR-29 family in particular, has emerged as a key regulator of liver fibrosis thus they may represent a novel target for therapeutic strategies against liver fibrosis (He et al.2012). The strong association of miRNAs with liver fibrosis brought insights into the potential of miRNAs as diagnostic and prognostic biomarkers. In a murine model of liver fibrosis induced by CCl4 treatment, the miR-29 family (miR-29a, miR-29b, miR-29c) was significantly down-regulated, whereas, miR-34 members (miR-34a, miR-34b and miR-34c) were found to be up-regulated. It was also demonstrated that miR-29a has a characteristic low levels in the serum of human patients having liver fibrosis (Roderburg et al.2011). Another study demonstrated the over-expression of miR-199 and miR-200 families in the progression of liver fibrosis (Murakami et al.2011). Recent study in human patients suggest the use of miR-122 and miR-200b for early diagnosis of liver fibrosis (López-Riera et al.2018). Several other studies have demonstrated dysregulation of miRNA in liver fibrosis as depicted in Tables 1 and 2.
Schisandrin B promotes senescence of activated hepatic stellate cell via NCOA4-mediated ferritinophagy
Published in Pharmaceutical Biology, 2023
Mingyue Ma, Na Wei, Jieren Yang, Tingting Ding, Anping Song, Lerong Chen, Shuguo Zheng, Huanhuan Jin
Hepatic fibrosis, a reversible wound-healing response triggered by a chronic liver injury, will eventually progress to liver cirrhosis, hepatocellular carcinoma and even liver failure if not treated properly (Schuppan and Kim 2013; Pellicoro et al. 2014; Forouzanfar et al. 2016). Hepatic fibrosis is mainly characterized by excessive deposition of extrahepatic matrix proteins and activation of hepatic stellate cells (HSCs). It is well known that activated HSCs are the principal cell type in the progression of liver fibrogenesis (Bataller and Brenner 2005) and intervention in the activation of HSCs has become an effective treatment measure. There have been a number of efforts to explore effective measures to control HSCs activation, including inhibiting HSCs proliferation, promoting HSCs apoptosis, autophagy or immune clearance (Zhang et al. 2014; Tsuchida and Friedman 2017). Recent studies revealed that induction of activated HSCs senescence was also an effective strategy for blocking the process of hepatic fibrosis (Krizhanovsky et al. 2008; Zhang et al. 2021). Cellular senescence, a response to different stresses, is a highly stable cell cycle arrest (Munoz-Espin and Serrano 2014), during which cells undergo some morphological, biochemical and functional changes including increased senescence-associated β-galactosidase (SA-β-gal) activity, DNA damage and the dysfunction of telomere and telomerase system (Bernadotte et al. 2016; Herranz and Gil 2018; Shmulevich and Shmulevic 2021).
Related Knowledge Centers
- Cytoglobin
- Cytoplasm
- Fibrosis
- Hepatocyte
- Pericyte
- Liver
- Perisinusoidal Space
- Liver Sinusoid
- Scar
- Chloroauric Acid