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In some pathological conditions, cells are exposed to high concentrations of glucose for extended periods. In this study, we investigated metabolic, oxidative stress, and cellular senescence pathways in human bronchial epithelial cells (HBECs) cultured in media with physiologically low (5\u2009m<jats:sc>m<\/jats:sc>) and high (12.5\u2009m<jats:sc>m<\/jats:sc>) glucose concentrations. HBECs exposed to 12.5\u2009m<jats:sc>m<\/jats:sc> glucose showed increased glucose routing toward the pentose phosphate pathway, lactate synthesis, and glycogen, but not triglyceride synthesis. These metabolic shifts were not associated with changes in cell proliferation rates, oxidative stress, or cellular senescence pathways. Since hyperglycemia is associated with fibrosis in the lung, we asked whether HBECS could activate fibroblasts. Primary human lung fibroblasts cultured in media conditioned by 12.5\u2009m<jats:sc>m<\/jats:sc> glucose\u2010exposed HBECs showed a 1.3\u2010fold increase in the gene expression of <jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic>, along with twofold increased protein levels of smooth muscle cell actin and 2.4\u2010fold of COL1A1. Consistently, HBECs cultured with 12.5\u2009m<jats:sc>m<\/jats:sc> glucose secreted proteins associated with inflammation and fibrosis, such as interleukins IL\u20101\u03b2, IL\u201010, and IL\u201013, CC chemokine ligands CCL2 and CCL24, and with extracellular matrix remodeling, such as metalloproteinases (MMP)\u20101, MMP\u20103, MMP\u20109, and MMP\u201013 and tissue inhibitors of MMPs (TIMP)\u20101 and \u20102. This study shows that HBECs undergo metabolic reprogramming and increase the secretion of profibrotic mediators following exposure to high concentrations of glucose, and it contributes to the understanding of the metabolic crosstalk of neighboring cells in diabetes\u2010associated pulmonary fibrosis.<\/jats:p>","DOI":"10.1002\/2211-5463.13852","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T05:50:42Z","timestamp":1719899442000},"page":"1441-1454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular glucose triggers metabolic reprogramming of cultured human bronchial epithelial cells and indirect fibroblast activation"],"prefix":"10.1002","volume":"14","author":[{"given":"Sangmi S.","family":"Park","sequence":"first","affiliation":[{"name":"Department of Cell Biology State University of New York Downstate Health Sciences University  Brooklyn NY 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