Abstract
Extracellular matrix glycoprotein tenascin‑X (TNX) is the largest member of the tenascin family. In the present study, the contribution of TNX to liver dysfunction was investigated by administration of high‑fat and high‑cholesterol diet with high levels of phosphorus and calcium (HFCD) to wild‑type (WT) and TNX‑knockout (KO) mice. After 16 weeks of HFCD administration, the ratio of liver weight to body weight was approximately 22% higher in the HFCD‑fed WT mice compared with the HFCD‑fed TNX‑KO mice, indicating hepatomegaly in HFCD‑fed WT mice. Histological analyses with hematoxylin and eosin staining at 21 weeks revealed that hepatocyte hypertrophy in HFCD‑fed TNX‑KO mice was suppressed to 85% of that in HFCD‑fed WT mice. By contrast, there was a 1.2‑fold increase in lipid deposition in hepatocytes from HFCD‑fed TNX‑KO mice compared with HFCD‑fed WT mice at 18 weeks, as demonstrated by Oil Red O staining. In addition, TNX‑KO mice at 21 weeks and 27 weeks post‑HFCD administration exhibited significant suppression of inflammatory cell infiltrate to 51 and 24% of that in WT mice, respectively. Immunofluorescence analysis for type I collagen and Elastica van Gieson staining demonstrated a clear hepatic fibrosis progression in HFCD‑fed WT mice at 27 weeks, whereas hepatic fibrosis was undetected in HFCD‑fed TNX‑KO mice. The present findings indicated that TNX deficiency suppressed hepatic dysfunction induced by HFCD administration.