HSF4 transcriptional regulates HMOX-1 expression in HLECs.

The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4) is a cataract-causing gene and plays important roles during lens development. Here we show that HMOX-1, an anti-oxidase, is a bona fide transcriptional target gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein accumulation. The HSE element located at the region of -389 bp to -362 bp upstream from the TSS (transcription start site), which is critical for HMOX-1 transcriptional activation. Furthermore, knockdown of HSF4 by siRNA inhibited HMOX-1 expression. Thus, these data revealed a novel transcription target of HSF4 and provided new insights into anti-oxidation regulation in lens and age-related cataract.