TY - JOUR
T1 - Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis
AU - Kumar, Santosh
AU - Duan, Qihua
AU - Wu, Rongxue
AU - Harris, Edward N.
AU - Su, Qiaozhu
N1 - Funding Information:
This work was supported by a grant from British Heart Foundation (UK) (PG/19/86134788) and a grant from Northern Ireland Chest Heart & Stroke (2019_08) to Q. Su; National Institutes of Health grant HL130864 to E. Harris.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9
Y1 - 2021/9
N2 - Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease that encompasses a spectrum of pathological conditions, ranging from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), fibrosis/cirrhosis which can further progress to hepatocellular carcinoma and liver failure. The progression of NAFL to NASH and liver fibrosis is closely associated with a series of liver injury resulting from lipotoxicity, oxidative stress, redox imbalance (excessive nitric oxide), ER stress, inflammation and apoptosis that occur sequentially in different liver cells which ultimately leads to the activation of liver regeneration and fibrogenesis, augmenting collagen and extracellular matrix deposition and promoting liver fibrosis and cirrhosis. Type 2 diabetes is a significant risk factor in NAFLD development by accelerating liver damage. Here, we overview recent findings from human study and animal models on the pathophysiological communication among hepatocytes (HCs), Kupffer cells (KCs), hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the disease development. The mechanisms of crucial signaling pathways, including Toll-like receptor, TGFβ and hedgehog mediated hepatic injury are also discussed. We further highlight the potentials of precisely targeting hepatic individual cell-type using nanotechnology as therapeutic strategy for the treatment of NASH and liver fibrosis.
AB - Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease that encompasses a spectrum of pathological conditions, ranging from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), fibrosis/cirrhosis which can further progress to hepatocellular carcinoma and liver failure. The progression of NAFL to NASH and liver fibrosis is closely associated with a series of liver injury resulting from lipotoxicity, oxidative stress, redox imbalance (excessive nitric oxide), ER stress, inflammation and apoptosis that occur sequentially in different liver cells which ultimately leads to the activation of liver regeneration and fibrogenesis, augmenting collagen and extracellular matrix deposition and promoting liver fibrosis and cirrhosis. Type 2 diabetes is a significant risk factor in NAFLD development by accelerating liver damage. Here, we overview recent findings from human study and animal models on the pathophysiological communication among hepatocytes (HCs), Kupffer cells (KCs), hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the disease development. The mechanisms of crucial signaling pathways, including Toll-like receptor, TGFβ and hedgehog mediated hepatic injury are also discussed. We further highlight the potentials of precisely targeting hepatic individual cell-type using nanotechnology as therapeutic strategy for the treatment of NASH and liver fibrosis.
KW - ER stress
KW - Hedgehog and TGFβ
KW - Lipotoxicity
KW - Liver fibrosis
KW - Metabolic inflammation
KW - NAFLD
KW - NASH
KW - Nitric oxide
KW - Oxidative stress
KW - TLRs
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U2 - 10.1016/j.addr.2021.113869
DO - 10.1016/j.addr.2021.113869
M3 - Review article
C2 - 34280515
AN - SCOPUS:85111582948
SN - 0169-409X
VL - 176
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
M1 - 113869
ER -