Data from Dual impact of IGF2 on alveolar stem cell function during tobacco-induced injury repair and development of pulmonary emphysema and cancer Article Swipe

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Hye‐Jin Boo , Hye‐Young Min , Choon-Sik Park , Jong‐Sook Park , Ji Yun Jeong , Shin Yup Lee , Woo‐Young Kim , Jae‐Won Lee , Sei‐Ryang Oh , Rang‐Woon Park , Ho‐Young Lee ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1158/0008-5472.c.6653426.v3

Pulmonary emphysema is a destructive inflammatory disease primarily caused by cigarette smoking (CS). Recovery from CS-induced injury requires proper stem cell (SC) activities with a tightly controlled balance of proliferation and differentiation. Here we show that acute alveolar injury induced by two representative tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (N/B), increased IGF2 expression in alveolar type 2 cells (AT2s) to promote their SC function and facilitate alveolar regeneration. Autocrine IGF2 signaling upregulated Wnt genes, particularly Wnt3, to stimulate AT2 proliferation and alveolar barrier regeneration after N/B-induced acute injury. In contrast, repetitive N/B exposure provoked sustained IGF2-Wnt signaling through DNMT3A-mediated epigenetic control of IGF2 expression, causing a proliferation/differentiation imbalance in AT2s and development of emphysema and cancer. Hypermethylation of the IGF2 promoter and overexpression of DNMT3A, IGF2, and the Wnt target gene AXIN2 were seen in the lungs of patients with CS-associated emphysema and cancer. Pharmacological or genetic approaches targeting IGF2-Wnt signaling or DNMT prevented the development of N/B-induced pulmonary diseases. These findings support dual roles of AT2 cells, which can either stimulate alveolar repair or promote emphysema and cancer depending on IGF2 expression levels.

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Lung cancer Medicine Dual (grammatical number) Pulmonary function testing Pulmonary emphysema Pathology Internal medicine Lung Literature Art

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/0008-5472.c.6653426.v3
OA Status: gold
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OpenAlex ID: https://openalex.org/W4402806482

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DOI: https://doi.org/10.1158/0008-5472.c.6653426.v3

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Title: Data from Dual impact of IGF2 on alveolar stem cell function during tobacco-induced injury repair and development of pulmonary emphysema and cancer

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Type: preprint

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Language: en

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Publication year: 2024

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Publication date: 2024-09-16

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Authors: Hye‐Jin Boo, Hye‐Young Min, Choon-Sik Park, Jong‐Sook Park, Ji Yun Jeong, Shin Yup Lee, Woo‐Young Kim, Jae‐Won Lee, Sei‐Ryang Oh, Rang‐Woon Park, Ho‐Young Lee

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Landing page: https://doi.org/10.1158/0008-5472.c.6653426.v3

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OA URL: https://doi.org/10.1158/0008-5472.c.6653426.v3

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Concepts: Lung cancer, Medicine, Dual (grammatical number), Pulmonary function testing, Pulmonary emphysema, Pathology, Internal medicine, Lung, Literature, Art

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