Adrenomedullin Deficiency Potentiates Lipopolysaccharide-Induced Experimental Bronchopulmonary Dysplasia in Neonatal Mice

Leveraging Integrated RNA Sequencing to Decipher Adrenomedullin’s Protective Mechanisms in Experimental Bronchopulmonary Dysplasia

“…To validate the bulk RNA-seq data generated in this study, we compared the results of the RNA-seq data with the RNA and protein expression data from our previous study in Adm +/ − and WT mice exposed to LPS or PBS [ 48 ]. In the previous study, the RNA and protein expression changes for select genes were quantified using quantitative polymerase chain reaction (qPCR) and immunoblotting studies in Adm +/ − and WT mice using the same LPS-induced experimental BPD model [ 48 ]. Increased up-regulation of genes Ccl2 , Ccl3 , Cxcl1 , Icam1 , Il1b , and Tnf in Adm +/ − compared to WT mice was confirmed by the previous qPCR study results ( Figure 2 A) [ 48 ].…”

“…For the LPS treatment, we administered intraperitoneal injections of 6 mg/kg of Escherichia coli O55:B5 LPS (Sigma-Aldrich, St. Louis, MO, USA; L2880) or an equivalent volume of PBS to both wild-type (WT) or Adm +/+ and Adm +/− mice once daily for three days on postnatal days (Ps) 3–5 [ 48 ].…”

“…Others and ourselves have highlighted the protective role of Adm in preclinical BPD studies. Insults such as hyperoxia and lipopolysaccharide (LPS) alter Adm expression and signaling in the developing lungs of rodents [ 44 , 45 , 46 , 47 , 48 ]. Further, BPD infants also have higher Adm expression compared to non-BPD infants [ 49 ].…”

“…Further, BPD infants also have higher Adm expression compared to non-BPD infants [ 49 ]. Yet, decreased Adm expression or signaling causes or augments BPD phenotype [ 45 , 47 , 48 ], and Adm peptide treatment mitigates experimental BPD [ 47 ]. These findings emphasize the protective role of Adm in neonatal lungs and its potential to serve as a biomarker and therapeutic target for BPD infants.…”

“…Identifying these mechanisms holds promise for developing precise prediction models and therapies for the disease. Therefore, we performed unbiased bulk RNA sequencing of the lungs from Adm -sufficient and haplodeficient mice in a well-established LPS-induced model of experimental BPD [ 48 ] and integrated bulk RNA sequencing results with state-of-the-art single-cell lung atlas studies to resolve how Adm protects neonatal lungs against chronic injury.…”