Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis
Enis Kostallari, Bo Wei, Delphine Sicard, Jiahui Li, Shawna A. Cooper, Jinhang Gao, Mrunal Dehankar, Ying Li, Sheng Cao, Meng Yin, Daniel J. Tschumperlin, Vijay H. Shah
2021American Journal of Physiology-Gastrointestinal and Liver Physiology56 citationsDOIOpen Access PDF
Abstract
The fibrogenic wound-healing response in liver increases stiffness. Here, macro and microheterogeneity of liver stiffness correlate with HSC heterogeneity in a hepatic fibrosis mouse model. Fibrogenic HSCs localized in stiff collagen-high areas upregulate the expression of focal adhesion molecule FHL2, which, in turn, promotes extracellular matrix protein expression. These results demonstrate that stiffness heterogeneity at the whole organ, lobular, and cellular level drives an amplification loop of fibrogenesis through specific focal adhesion molecular pathways.
Topics & Concepts
Extracellular matrixHepatic stellate cellFibrosisDownregulation and upregulationFocal adhesionHepatic fibrosisCell biologyCell adhesion moleculeLiver fibrosisPathologyType I collagenCancer researchBiologyChemistryMedicineSignal transductionGeneBiochemistryLiver physiology and pathologyCellular Mechanics and InteractionsLiver Disease Diagnosis and Treatment