Fig 1: N-acetyl-lysyltyrosylcysteine-amide (KYC) attenuates ER stress in HOX and Tun-treated neonatal lungs with improved alveolar formation.(A) All ER stress markers in the HOX lungs (P-PERK 0.4±0.2-fold; P-IRE1a 0.4±0.2-fold; GRP78 0.5±0.1-fold; cleaved ATF6 0.3±0.2-fold; spliced XBP1 0.4±0.4-fold; CHOP 0.4±0.3-fold) decrease significantly by KYC (n = 12, p<0.05, 6 for each sex). (B) KYC improves the ER dilation in EC and AT2 of the HOX lungs. (C) KYC decreases ER stress markers (P-PERK 0.5±0.1-fold; P-IRE1a 0.6±0.1-fold; GRP78 0.7±0.3-fold; spliced XBP1 0.6±0.2-fold; cleaved ATF6 0.5±0.4-fold) and ER stress-mediated apoptosis (CHOP 0.8±0.1-fold; cleaved caspase-12 0.5±0.1-fold; BAX/BCl2 ratio 0.7±0.1-fold) in Tun-treated neonatal lungs (n = 6, p<0.05). But levels of N-glycosylated VEGFR2 are significantly increased (1.4±0.3-fold) by KYC. (D) KYC decreases the DRP1 expressions (0.5±0.1-fold) and improves the ER-mitochondria contact, as shown by the increased expressions of GRP75 (1.5±0.2-fold) and ACSL4 (1.7±0.7-fold). (E) KYC significantly decreases MPO expression levels (0.7±0.1-fold) in the Tun-treated lungs. (F) Although KYC does not improve the weight gain in Tun-treated rat pups, it still improves the alveolar formation (MLI 76.8±5.9 vs. 94.2±8.4 µm; RAC 4.3±0.3 vs. 3.8±0.3; secondary septation 38.7±4.9 vs. 25.2±4.1; n = 12, p<0.05). LB: lamellar body; M: mitochondria. *: p<0.05; scale bar = 500 nm.