Compositions and methods for treating liver disease

Compositions and methods for treating liver disease in a subject by increasing the transport or retention of transcription factor HNF4 [alpha] into the nucleus of liver cells in the subject are disclosed. In some embodiments, the methods comprise upregulating the expression or function of one or more transcription factors selected from the group consisting of PROX1, NR5A2, NR0B2, MTF1, SREBP1, EP300 and POM121C and functional fragments thereof, and/or down-regulating the expression or function of one or more transcription factors selected from the group consisting of DNAJB1/HSP40, ATF6, ATF4 and PERK and functional fragments thereof. 公开了通过增加转录因子HNF4α到受试者的肝细胞的核中的转运或保留来治疗受试者肝病的组合物和方法。在一些实施方式中，所述方法包括上调一种或多种选自由PROX1、NR5A2、NR0B2、MTF1、SREBP1、EP300和POM121C组成的组的转录因子及其功能性片段的表达或功能，和/或下调一种或多种选自DNAJB1/HSP40、ATF6、ATF4和PERK的转录因子及其功能性片段的表达或功能。