Wilms Tumor 1 Associated Protein (WTAP) Inhibits Inflammation Provoked by Mycobacterium tuberculosis in Microglial BV-2 Cells and Promotes Differentiation of Neural Stem/Progenitor Cells into Neurons by Elevating Expression of HMGN3 Protein Resulted from Modulation of m6A Metilation of Its RNA.

Tuberculous meningitis (TBM) is the most prevalent and severe manifestation of tuberculosis in CNS. The mechanisms of neurological injury caused by TBM are not well understood. Our study showed that overexpression of WTAP (Wilms tumor 1 associated protein) reduced inflammatory factors and Iba-1 expression induced in BV-2 by H37Rv. It also increased proliferation of neural stem/progenitor cells (NSPCs) and expression of the neuronal marker DCX in these cells. WTAP enhanced expression of high mobility group nucleosome-binding domain-containing protein 3 (HMGN3) by promoting m6A methylation of its mRNA. Reducing HMGN3 expression negated WTAP-induced anti-inflammatory and neuroprotective effects in TBM cell model. WTAP inhibited inflammation and microglia activation while promoting NSPC differentiation into neurons via elevation of HMGN3 expression. WTAP/HMGN3 proteins and the corresponding mRNA could be potential targets in the treatment of TBM.