Targeting an ALKBH5-IL11 receptor axis for cardiac fibrosis

Inhibiting the RNA N6-methylasdenosine (m6A) demethylase ALKBH5 or the IL-11 receptor could help treat cardiac fibrosis by increasing m6A modifications on IL-11 mRNA, which decreases IL-11 stability, and prevents IL-11 pathway activation in cardiac macrophages, thus limiting macrophage-to-myofibroblast transition and fibrosis.

Single cell RNA sequencing and lineage tracing analyses showed higher levels of macrophage-to-myofibroblast transition in cardiac monocyte-derived macrophages (MDMs) from mice with angiotensin II-induced hypertension than in MDMs from healthy control. The analysis also identified ALKBH5 and IL-11 receptor, whose expression was higher in MDMs from mice with hypertension, as candidate regulators of that process. ...