Hepatic lipid accumulation induced by mono-(2-ethylhexyl) phthalate and potential ERBB2-associated inflammatory...

The primary active metabolite of di (2-ethylhexyl) phthalate (DEHP), mono (2-ethylhexyl) phthalate (MEHP), has received increasing attention due to its association with metabolic liver injury. However, the mechanisms underlying its involvement in nonalcoholic fatty liver disease remain poorly understood.

This study employed an integrative approach combining network toxicology, machine learning, and molecular docking analyses to systematically investigate the potential molecular mechanisms of MEHP-related NAFLD and to identify candidate targets potentially involved in disease progression. Immune infiltration analysis and in vitro experiments were conducted to further validate the functions of the candidate targets.

Multidimensional analyses identified ERBB2 as a candidate gene worthy of further investigation. Immune infiltration analysis suggested that ERBB2 may be associated with alterations in the hepatic immune microenvironment, whereas molecular docking analysis indicated a potential interaction between MEHP and ERBB2. Further in vitro experiments showed that MEHP exposure increased ERBB2 protein expression, accompanied by elevated levels of inflammation-related proteins, including TNF-α, IL-6, and IL-1β. Collectively, these findings suggest that ERBB2 may be related to MEHP exposure-associated inflammatory molecular alterations and regulation of the hepatic immune microenvironment.

From the perspective of inflammation and immune regulation, this study proposes that ERBB2 may be involved in MEHP-induced NAFLD, providing a new theoretical basis for toxicological research on environment-related NAFLD.