Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis

Santosh Kumar, Qihua Duan, Rongxue Wu, Edward N Harris, Qiaozhu Su

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.
Original languageEnglish
Article number113869
JournalAdvanced Drug Delivery Reviews
Volume176
Early online date16 Jul 2021
DOIs
Publication statusPublished - Sep 2021

Keywords

  • NASH
  • TLRs
  • Liver fibrosis
  • ER stress
  • NAFLD
  • Lipotoxicity
  • Nitric oxide
  • Oxidative stress
  • Hedgehog and TGFβ
  • Metabolic inflammation

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