SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection

Abstract

New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function. The host factors that relinquish restoration of lung health to enduring lung injury are insufficiently understood. Here, we investigated the role of endophilin B2 (B2) in susceptibility to severe influenza infection. WT and B2-deficient mice were infected with H1N1 PR8 by intranasal administration and course of influenza pneumonia, inflammatory, and tissue responses were monitored over time. Disruption of B2 enhanced recovery from severe influenza infection as indicated by swift body weight recovery and significantly better survival of endophilin B2-deficient mice compared to WT mice. Compared to WT mice, the B2-deficient lungs exhibited induction of genes that express surfactant proteins, ABCA3, GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of CCAAT/enhancer binding protein CEBPα, β, and δ mRNAs 3–14 days after infection, and differences in alveolar extracellular matrix integrity and respiratory mechanics. Flow cytometry and gene expression studies demonstrated robust recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in B2-deficient lungs. Targeting of endophilin B2 alleviates adverse effects of IAV infection on respiratory and immune cells enabling restoration of alveolar homeostasis.

Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer

“…Our data supported the tumor suppressor role of SH3GLB1 in colorectal cancer. During tumor development and progression, protein interactions between SH3GLB1 and BAX resulted in the activation of caspase 3, thereby inducing apoptosis[ 30 ]. Similarly, we showed that lncRP4-induced SH3GLB1 upregulation increased levels of BAX and caspase 3 in colorectal cancer cells.…”

Modulation of the lung inflammatory response to ozone by the estrous cycle

“…We obtained respiratory mechanics parameters following administration of 0–50 mg/mL of methacholine (Sigma‐Aldrich, St Louis, MO), as described in Fino et al. (). We recovered BAL cells in 2.5 mL of DPBS with 1 mmol/L EDTA and analyzed as described in Cabello et al.…”

“…1), we anesthetized mice with ketamine, (130 mg/kg), xylazine (10 mg/kg), and vecuronium bromide (1 mg/kg) i.p., and connected them to a flexiVent system (SCIREQ Inc, Canada) at a respiratory rate of 150 breaths/min and a positive end-expiratory pressure of 3 cm H 2 O. We obtained respiratory mechanics parameters following administration of 0-50 mg/mL of methacholine (Sigma-Aldrich, St Louis, MO), as described in Fino et al (2017). We recovered BAL cells in 2.5 mL of DPBS with 1 mmol/L EDTA and analyzed as described in Cabello et al (2015).…”

Innate Immune Cell Suppression and the Link With Secondary Lung Bacterial Pneumonia

“…Analysis of RNA datasets from patients infected with pandemic associated influenza strains shows that H5N1 and H7N9 infection are enriched for genes involved with the extracellular matrix pathway (228). The importance of lung recovery and resilience is also demonstrated in mice lacking endophilin B2 that display improved mechanosensing and collagen and elastin ECM remodeling compared to wild-type mice (229). There are many other examples where matrix and associated components impact on lung immunity, which have been comprehensively reviewed elsewhere (230).…”