The transcription factor hepatocyte nuclear factor 4α (HNF4A) is critical for maintaining epithelial differentiation and mature function in renal proximal tubules (PTs). The researchers investigated HNF4A dynamics during acute and chronic human kidney disease and in cultured primary proximal tubular epithelial cells (PTECs). Immunohistochemical analyses revealed a reciprocal relationship between the loss of HNF4A and the gain of vimentin expression in injured kidneys, reflecting PT dedifferentiation. In vitro, primary PTECs rapidly downregulated HNF4A and proximal tubular markers while upregulating vimentin during subculture. Adenoviral-mediated re-expression of HNF4A using Creative Biogene's human HNF4A adenovirus restored transcripts associated with brush border formation and absorptive/transport functions, as confirmed by RNA sequencing and gene set enrichment analyses, providing a robust model to study PT injury and regeneration mechanisms.
Figure 1. Immunohistochemistry and in vitro culture demonstrated that HNF4A expression declines while vimentin levels increase in primary PTECs, reflecting PT dedifferentiation during kidney injury and cell culture. (Kha M, et al., 2025)