Understanding the cellular interactome of non-alcoholic fatty liver disease

Serum CXCL5 Detects Early Hepatocellular Carcinoma and Indicates Tumor Progression

“…In this context, (resident) macrophages represent the major source of cytokines and chemokines upon liver injury, attracting further immune cells and shaping the local microenvironment [ 35 ]. Recent studies highlight the heterogeneity as well as the disease-specific, context-dependent plasticity of phagocytes and their functional consequences [ 36 ]. Therefore, during carcinogenesis, the pro- and anti-inflammatory properties of macrophages can specifically shape the TME but can also be exploited by the tumor [ 37 ].…”

Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma

“…Single cell transcriptomic analysis of human NASH samples showed that injured hepatocytes stimulate myofibroblast differentiation and activation through TGFβ-1/2, Sonic hedgehog, and PDGFRBB signaling, which implicates the interplay between hepatocytes and activated fibroblasts in development of NASH-induced HCC. 100 By examining the single cell expression profiles of HSCs extracted from a NASH model derived from foz / foz mice fed with western diet, heterogeneity of HSC was observed with 4 well-defined clusters with distinct functions. 101 In patients with NASH-induced HCC, increased senescence and senescence-associated secretory phenotype were observed in CAFs, as evidenced by the increase in expression of α-SMA, p21, γ-H2AX, and IL-6.…”

Modeling Nonalcoholic Fatty Liver Disease in the Dish Using Human-Specific Platforms: Strategies and Limitations

“… 2 This cascade of events activates liver resident macrophages (ie, Kupffer cells [KCs]) and liver sinusoidal endothelial cells (LSECs) to secrete a wide range of chemokines to recruit circulating myeloid and lymphoid immune cells. 3 , 4 , 5 , 6 The complex inflammatory response triggers the differentiation of hepatic stellate cells (HSCs) into myofibroblasts responsible for extracellular matrix deposition unless the injury subsides. As relevant for patient-specific models, genetic polymorphisms can determine the risk for NAFLD and its progression.…”