Transmembrane protein TMEM97 and epigenetic reader BAHCC1 constitute an axis that supports pro-inflammatory cytokine expression

Cell Signal. 2024 Jan 28;116:111069. doi: 10.1016/j.cellsig.2024.111069. Online ahead of print.ABSTRACTPro-inflammatory cytokine production by the retinal pigment epithelium (RPE) is a key etiology in retinal degenerative diseases, yet the underlying mechanisms are not well understood. TMEM97 is a scarcely studied transmembrane protein recently implicated in retinal degeneration. BAH domain coiled coil 1 (BAHCC1) is a newly discovered histone code reader involved in oncogenesis. A role for TMEM97 and BAHCC1 in RPE inflammation was not known. Here we found that they constitute a novel axis regulating pro-inflammatory cytokine expression in RPE cells. Transcriptomic analysis using a TMEM97-/- ARPE19 human cell line and the validation via TMEM97 loss- and gain-of-function revealed a profound role of TMEM97 in promoting the expression of pro-inflammatory cytokines, notably IL1β and CCL2, and unexpectedly BAHCC1 as well. Moreover, co-immunoprecipitation indicated an association between the TMEM97 and BAHCC1 proteins. While TMEM97 ablation decreased and its overexpression increased NFκB (p50, p52, p65), the master transcription factor for pro-inflammatory cytokines, silencing BAHCC1 down-regulated NFκB and downstream pro-inflammatory cytokines. Furthermore, in an RPE-damage retinal degeneration mouse model, immunofluorescence illustrated down-regulation of IL1β and CCL2 total proteins and suppression of glial activation in the retina of Tmem97-/- mice compared to Tmem97+/+ mice...
Source: Cellular Signalling - Category: Cytology Authors: Source Type: research