Perinatal nicotine exposure alters lung development and induces HMGB1-RAGE expression in neonatal mice

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5 Citations (Scopus)


Background: Maternal nicotine exposure during gestation and lactation adversely affect lung development of their children. High-mobility group box 1 (HMGB1) is the encoded non-histone, nuclear DNA-binding protein that regulates transcription, and is involved in organization of DNA. Receptors for advanced glycation end products (RAGE) is a receptor for HMGB1 and activates nuclear factor-κB (NF-κB) signaling. Animal and human studies have found cigarette smoke exposure upregulates RAGE expression, suggesting that the HMGB1-RAGE pathway might be involved in maternal nicotine-induced lung injury. Methods: This study evaluated prenatal and perinatal nicotine effects on lung development and HMGB1 and RAGE expression in mouse offspring. Nicotine was administered to pregnant mice by subcutaneous osmotic mini-pump at a dose of 6 mg kg−1 day−1 from gestational Day 14 to birth (prenatal) or to postnatal Day 21 (perinatal). A control group received an equal volume of saline by the same route. Three study groups were obtained: prenatal normal saline (NS), prenatal nicotine, and perinatal nicotine groups. The mice were euthanized on postnatal Day 21, and the lung tissues were collected for histological and Western blot analyses. Results: Mice exposed to prenatal nicotine exhibited significantly higher lung mean chord length and oxidative stress marker 8-hydroxy-2′-deoxyguanosine and NF-κB expression compared to mice exposed to NS. Perinatal nicotine exposure further enhanced these harmful effects. These perinatal nicotine effects on lung development were associated with increased HMGB1 and RAGE expression. Conclusions: HMGB1-RAGE pathway may be involved in the pathogenesis of altered lung development induced by perinatal nicotine exposure.

Original languageEnglish
Pages (from-to)570-578
Number of pages9
JournalBirth Defects Research
Issue number7
Publication statusPublished - Apr 15 2021


  • 8-hydroxy-2′-deoxyguanosine
  • high-mobility group box 1
  • mean chord length
  • nicotine
  • nuclear factor-κB
  • receptors for advanced glycation end products

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis


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