Ac‐ SDKP Attenuates Silica‐Induced Pulmonary Fibrosis by Inhibiting ALKBH1 ‐Mediated m ⁶ A Demethylation of miR‐129‐5p

Silicosis, one of the most common and severe forms of pneumoconiosis, remains a major occupational health concern worldwide. Given the lack of effective therapies, understanding the underlying molecular mechanisms is urgently needed. Here, we report that ALKB homolog 1 (ALKBH1), an N6‐methyladenosine (m 6 A) demethylase, is upregulated in silica‐induced pulmonary fibrosis and plays a pro‐fibrotic role. The antifibrotic peptide Ac‐SDKP inhibited Alkbh1 expression and alleviated pulmonary fibrosis. Mechanistically, ALKBH1 suppressed the biosynthesis of miR‐129‐5p by removing m 6 A modification from pri‐miR‐129‐5p , thereby reducing DGCR8‐mediated processing and leading to decreased mature miR‐129‐5p levels. Ac‐SDKP reversed this process, restoring miR‐129‐5p expression. Functionally, overexpression of miR‐129‐5p attenuated silica‐induced pulmonary fibrosis by suppressing macrophage activation. Collectively, these findings identify the Ac‐SDKP‐ALKBH1‐ miR‐129‐5p axis as a critical regulatory mechanism, with ALKBH1‐mediated m 6 A demethylation of pri‐miR‐129‐5p representing a key node and a promising therapeutic target for silicosis.