tetano
Editor, Senior Moderator
Respir Res
. 2025 Mar 22;26(1):111.
doi: 10.1186/s12931-025-03187-9. Alveolar epithelial type 2 cell specific loss of IGFBP2 activates inflammation in COVID-19
Valentina Pujadas[SUP] 1 2 [/SUP], Chiahsuan Chin[SUP] 1 2 [/SUP], Narendra V Sankpal[SUP] 1 2 [/SUP], James Buhrmaster[SUP] 1 2 [/SUP], Ashwini Arjuna[SUP] 1 2 [/SUP], Rajat Walia[SUP] 1 2 [/SUP], Michael A Smith[SUP] 1 2 [/SUP], Oliver Eickelberg[SUP] 3 [/SUP], Ross M Bremner[SUP] 1 2 [/SUP], Thalachallour Mohanakumar[SUP] 1 2 [/SUP], Angara Sureshbabu[SUP] 4 5 [/SUP]
Affiliations
The coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, our understanding of SARS-CoV-2-induced inflammation in alveolar epithelial cells remains very limited. The contributions of intracellular insulin-like growth factor binding protein-2 (IGFBP2) to SARS-CoV-2 pathogenesis are also unclear. In this study, we have uncovered a critical role for IGFBP2, specifically in alveolar epithelial type 2 cells (AEC2), in the immunopathogenesis of COVID-19. Using bulk RNA sequencing, we show that IGFBP2 mRNA expression is significantly downregulated in primary AEC2 cells isolated from fibrotic lung regions from patients with COVID-19-acute respiratory distress syndrome (ARDS) compared to those with idiopathic pulmonary fibrosis (IPF) alone or IPF with a history of COVID-19. Using multicolor immunohistochemistry, we demonstrated that IGFBP2 and its selective ligands IGF1 and IGF2 were significantly reduced in AEC2 cells from patients with COVID-ARDS, IPF alone, or IPF with COVID history than in those from age-matched donor controls. Further, we demonstrated that lentiviral expression of Igfbp2 significantly reduced mRNA expression of proinflammatory cytokines-Tnf-α, Il1β, Il6, Stat3, Stat6 and chemokine receptors-Ccr2 and Ccr5-in mouse lung epithelial cells challenged with SARS-CoV-2 spike protein injury (S2; 500 ng/mL). Finally, we demonstrated higher levels of cytokines-TNF-α; IL-6 and chemokine receptor-CCR5 in AEC2 cells from COVID-ARDS patients compared to the IPF alone and the IPF with COVID history patients. Altogether, these data suggest that anti-inflammatory properties of IGFBP2 in AEC2 cells and its localized delivery may serve as potential therapeutic strategy for patients with COVID-19.
. 2025 Mar 22;26(1):111.
doi: 10.1186/s12931-025-03187-9. Alveolar epithelial type 2 cell specific loss of IGFBP2 activates inflammation in COVID-19
Valentina Pujadas[SUP] 1 2 [/SUP], Chiahsuan Chin[SUP] 1 2 [/SUP], Narendra V Sankpal[SUP] 1 2 [/SUP], James Buhrmaster[SUP] 1 2 [/SUP], Ashwini Arjuna[SUP] 1 2 [/SUP], Rajat Walia[SUP] 1 2 [/SUP], Michael A Smith[SUP] 1 2 [/SUP], Oliver Eickelberg[SUP] 3 [/SUP], Ross M Bremner[SUP] 1 2 [/SUP], Thalachallour Mohanakumar[SUP] 1 2 [/SUP], Angara Sureshbabu[SUP] 4 5 [/SUP]
Affiliations
- PMID: 40121473
- DOI: 10.1186/s12931-025-03187-9
The coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, our understanding of SARS-CoV-2-induced inflammation in alveolar epithelial cells remains very limited. The contributions of intracellular insulin-like growth factor binding protein-2 (IGFBP2) to SARS-CoV-2 pathogenesis are also unclear. In this study, we have uncovered a critical role for IGFBP2, specifically in alveolar epithelial type 2 cells (AEC2), in the immunopathogenesis of COVID-19. Using bulk RNA sequencing, we show that IGFBP2 mRNA expression is significantly downregulated in primary AEC2 cells isolated from fibrotic lung regions from patients with COVID-19-acute respiratory distress syndrome (ARDS) compared to those with idiopathic pulmonary fibrosis (IPF) alone or IPF with a history of COVID-19. Using multicolor immunohistochemistry, we demonstrated that IGFBP2 and its selective ligands IGF1 and IGF2 were significantly reduced in AEC2 cells from patients with COVID-ARDS, IPF alone, or IPF with COVID history than in those from age-matched donor controls. Further, we demonstrated that lentiviral expression of Igfbp2 significantly reduced mRNA expression of proinflammatory cytokines-Tnf-α, Il1β, Il6, Stat3, Stat6 and chemokine receptors-Ccr2 and Ccr5-in mouse lung epithelial cells challenged with SARS-CoV-2 spike protein injury (S2; 500 ng/mL). Finally, we demonstrated higher levels of cytokines-TNF-α; IL-6 and chemokine receptor-CCR5 in AEC2 cells from COVID-ARDS patients compared to the IPF alone and the IPF with COVID history patients. Altogether, these data suggest that anti-inflammatory properties of IGFBP2 in AEC2 cells and its localized delivery may serve as potential therapeutic strategy for patients with COVID-19.