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Alternative pathways for CTSB regulation of macrophage scavenger receptor (MSR)

Determine whether cathepsin B (CTSB) regulates macrophage scavenger receptor types I and II (MSR-A) expression through molecular pathways other than direct protein–protein interaction, and elucidate any such mechanisms in human macrophages relevant to esophageal adenocarcinoma.

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Background

The authors report strong predicted docking between CTSB and MSR based on ZDOCK and bidirectional associations via Mendelian randomization analyses.

Despite these findings, they explicitly acknowledge uncertainty about whether CTSB might regulate MSR through other, non-docking pathways, indicating a need for mechanistic studies to resolve the regulatory route(s).

References

Furthermore, while strong docking between CTSB and MSR was identified using the ZDOCK model, the possibility that CTSB regulates MSR expression through other pathways cannot be excluded.

— Defining the relationship between cathepsin B and esophageal adenocarcinoma: conjoint analysis of Mendelian randomization, transcriptome-wide association studies, and single-cell RNA sequencing data (2504.01270 - Li et al., 2 Apr 2025) in Discussion (Limitations)