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Peptide Regulation of Gene Expression and Protein Synthesis in Bronchial Epithelium



Some studies have shown that peptides have high treatment potential due to their biological activity, harmlessness, and tissue-specific action. Tetrapeptide Ala-Asp-Glu-Leu (ADEL) was effective on models of acute bacterial lung inflammation, fibrosis, and toxic lung damage in several studies.


We measured Ki67, Mcl-1, p53, CD79, and NOS-3 protein levels in the 1st, 7th, and 14th passages of bronchoepithelial human embryonic cell cultures. Gene expression of NKX2-1, SCGB1A1, SCGB3A2, FOXA1, FOXA2, MUC4, MUC5AC, and SFTPA1 was measured by real-time polymerase chain reaction. Using the methods of spectrophotometry, viscometry, and circular dichroism, we studied the ADEL–DNA interaction in vitro.


Peptide ADEL regulates the levels of Ki67, Mcl-1, p53, CD79, and NOS-3 proteins in cell cultures of human bronchial epithelium in various passages. The strongest activating effect of peptide ADEL on bronchial epithelial cell proliferation through Ki67 and Mcl-1 was observed in “old” cell cultures. ADEL regulates the expression of genes involved in bronchial epithelium differentiation: NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2. ADEL also activates several genes, which reduced expression correlated with pathological lung development: MUC4, MUC5AC, and SFTPA1. Spectrophotometry, viscometry, and circular dichroism showed ADEL–DNA interaction, with a binding region in the major groove (N7 guanine).


ADEL can bind to specific DNA regions and regulate gene expression and synthesis of proteins involved in the differentiation and maintenance of functional activity of the bronchial epithelium. Through activation of some specific gene expression, peptide ADEL may protect the bronchial epithelium from pulmonary pathology. ADEL also may have a geroprotective effect on bronchial tissue.

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BAL fluid:

Bronchoalveolar fluid


Circular dichroism


Cluster of differentiation 79, CD79a and CD79b types are members of immunoglobulin superfamily and both activate B cells


CD79a molecule, immunoglobulin-associated alpha (gene)


Complementary DNA


Chronic obstructive pulmonary disease


Glyceraldehyde-3-phosphate dehydrogenase


Homeobox protein


Forkhead box protein A2


Forkhead box A1 gene


Forkhead box A2 gene


KEDW-NH2, Lys-Glu-Asp-Trp-NH2–peptide


Antigen KI-67 protein


Induced myeloid leukemia cell differentiation protein, inhibits apoptosis and enhances cell survival


Myeloid cell leukemia sequence 1 (BCL2-related) gene

miRNA 365:

Small noncoding RNAs, regulates NKX2-1


Marker of proliferation Ki-67 gene


Mucin 4, cell surface associated (gene)


Mucin 5AC, oligomeric mucus/gel-forming (gene)


Nitric oxide synthase 3


Nitric oxide synthase 3 gene


NK2 homeobox 1 protein also known as thyroid transcription factor 1


Homeobox protein Nkx-2.1, isoform 2 (gene)


Transmembrane protein of the Notch family, member 1, promotes differentiation


Secretoglobin, family 3A, member 2


Secretoglobin, family 1A, member 1 (uteroglobin) (gene)


Secretoglobin, family 3A, member 2 (gene)


Surfactant protein (gene)


Pulmonary surfactant-associated protein A1


Cellular tumor antigen p53, phosphoprotein p53 or tumor suppressor p53


Tumor protein p53 gene


Tumor necrosis factor alpha


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None of the authors has any conflict of interest related to this manuscript.

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Correspondence to A. Bernadotte.

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Khavinson, V.K., Tendler, S.M., Vanyushin, B.F. et al. Peptide Regulation of Gene Expression and Protein Synthesis in Bronchial Epithelium. Lung 192, 781–791 (2014).

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  • Tetrapeptide
  • Bronchial epithelium
  • Signal molecule
  • Gene expression
  • Peptide–DNA interaction
  • Cell culture
  • Geroprotection
  • Geroprotector
  • Anti-aging
  • Peptide
  • COPD
  • ADEL