Promising therapeutic intervention: Dietary supplementation with alphaKG reduces pulmonary fibrosis and ARDS pathogenesis in SARS-CoV-2-infected mice

Title : Promising therapeutic intervention: Dietary supplementation with alphaKG reduces pulmonary fibrosis and ARDS pathogenesis in SARS-CoV-2-infected mice

Abstract:

Our recent study elucidates the protective role of alpha-ketoglutarate (αKG) in suppressing thrombosis and inflammation in mice. This effect is mediated through augmentation of prolyl hydroxylase 2 (PHD2) activity, leading to inhibition of AKT phosphorylation and HIF1-α stabilization. Recently, we described that dietary αKG supplementation attenuated lung inflammation and improved the mice survivability against SARS-CoV-2 infection. In this study, we investigated the therapeutic potential of αKG in ameliorating pulmonary fibrosis in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in mice. Mice with acute infection developed pulmonary fibrosis, leading to ARDS pathophysiology limiting pO2 levels. We describe that supplementation with 1% αKG till 15 days post-infection (DPI) significantly reduced SARS-CoV-2 infection, and decreased inflammation and fibrosis markers like surfactant proteins B and C in the lungs and thus restoring pO2 levels. SARS-CoV-2 induced epithelial to mesenchymal transition (EMT) in the lung tissues. Notably, αKG supplementation effectively inhibited the EMT and rescued lung fibrosis by suppressing P-AKT and TGF-β, reduced ZEB-1 and vimentin, and rescued EMT. Our findings thus underscore the promising therapeutic potential of αKG in treating lung fibrosis in SARS-CoV-2-induced ARDS-like conditions.

Biography:

Garima Joshi, a Ph.D. scholar at the Regional Centre for Biotechnology (RCB). She works as a senior research fellow, and her research focuses on combating post-acute COVID-19 complications, especially pulmonary inflammation and fibrosis, through alpha-ketoglutarate supplementation. To drive this forward, she developed a unique SARS-CoV-2-induced ARDS mice model, enabling new insights. With four publications—three research articles and a review—she is committed to advancing science and sharing findings. She actively engage in scientific conferences, including the IUBMB RNA virus meeting (2022) and a human microbiome conference with a next-generation sequencing workshop (2023). These events have enriched her research perspective and facilitated valuable professional connections.