Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b
Background:. A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2023-08-01
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| Series: | Plastic and Reconstructive Surgery, Global Open |
| Online Access: | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000005202 |
| _version_ | 1797732720903716864 |
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| author | Yuumi Lee, MD Yuko Ito, MD, PhD Kohei Taniguchi, MD, PhD Takashi Nuri, MD, PhD SangWoong Lee, MD, PhD Koichi Ueda, MD, PhD |
| author_facet | Yuumi Lee, MD Yuko Ito, MD, PhD Kohei Taniguchi, MD, PhD Takashi Nuri, MD, PhD SangWoong Lee, MD, PhD Koichi Ueda, MD, PhD |
| author_sort | Yuumi Lee, MD |
| collection | DOAJ |
| description | Background:. A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In this study, we aimed to investigate the roles of the zones in the execution of the Warburg effect and identify which microRNAs regulate this phenomenon in keloid tissue.
Methods:. Eleven keloids from patients were used. Using immunohistochemical analysis, 179 nodules were randomly chosen from these keloids to identify glycolytic enzymes, autophagic markers, pyruvate kinase M (PKM) 1/2, and polypyrimidine tract binding protein 1 (PTBP1). Western blot and qRT-PCR tests were also performed for PKM, PTBP1, and microRNAs (miR-133b and miR-200b, c).
Results:. Immunohistochemical analysis showed that the expression of the autophagic (LC3, p62) and glycolytic (GLUT1, HK2) were significantly higher in the CZ than in the MZ. PKM2 expression was significantly higher than PKM1 expression in keloid nodules. Furthermore, PKM2 expression was higher in the CZ than in the MZ. However, PKM1 and PTBP1 expression levels were higher in the MZ than in the CZ. The qRT-PCR analysis showed that miR-133b-3p was moderately downregulated in the keloids compared with its expression in the normal skin tissue.
Conclusions:. The Warburg effect occurred individually in nodules. The MZ presented PKM2-positive fibroblasts produced by activated PTBP1. In the CZ, PKM2-positive fibroblasts produced lactate. MiR-133b-3p was predicted to control the Warburg effect in keloids. |
| first_indexed | 2024-03-12T12:18:37Z |
| format | Article |
| id | doaj.art-54b72efa406243c7910db1a27ccae8aa |
| institution | Directory Open Access Journal |
| issn | 2169-7574 |
| language | English |
| last_indexed | 2024-03-12T12:18:37Z |
| publishDate | 2023-08-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Plastic and Reconstructive Surgery, Global Open |
| spelling | doaj.art-54b72efa406243c7910db1a27ccae8aa2023-08-30T06:13:52ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742023-08-01118e520210.1097/GOX.0000000000005202202308000-00048Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133bYuumi Lee, MD0Yuko Ito, MD, PhD1Kohei Taniguchi, MD, PhD2Takashi Nuri, MD, PhD3SangWoong Lee, MD, PhD4Koichi Ueda, MD, PhD5From the * Department of Plastic and Reconstructive Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan† Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan‡ Center for Medical Research & Development, Division of Translational Research, Osaka Medical and Pharmaceutical University, Osaka, Japan.From the * Department of Plastic and Reconstructive Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan† Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Osaka, JapanFrom the * Department of Plastic and Reconstructive Surgery, Osaka Medical and Pharmaceutical University, Osaka, JapanBackground:. A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In this study, we aimed to investigate the roles of the zones in the execution of the Warburg effect and identify which microRNAs regulate this phenomenon in keloid tissue. Methods:. Eleven keloids from patients were used. Using immunohistochemical analysis, 179 nodules were randomly chosen from these keloids to identify glycolytic enzymes, autophagic markers, pyruvate kinase M (PKM) 1/2, and polypyrimidine tract binding protein 1 (PTBP1). Western blot and qRT-PCR tests were also performed for PKM, PTBP1, and microRNAs (miR-133b and miR-200b, c). Results:. Immunohistochemical analysis showed that the expression of the autophagic (LC3, p62) and glycolytic (GLUT1, HK2) were significantly higher in the CZ than in the MZ. PKM2 expression was significantly higher than PKM1 expression in keloid nodules. Furthermore, PKM2 expression was higher in the CZ than in the MZ. However, PKM1 and PTBP1 expression levels were higher in the MZ than in the CZ. The qRT-PCR analysis showed that miR-133b-3p was moderately downregulated in the keloids compared with its expression in the normal skin tissue. Conclusions:. The Warburg effect occurred individually in nodules. The MZ presented PKM2-positive fibroblasts produced by activated PTBP1. In the CZ, PKM2-positive fibroblasts produced lactate. MiR-133b-3p was predicted to control the Warburg effect in keloids.http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000005202 |
| spellingShingle | Yuumi Lee, MD Yuko Ito, MD, PhD Kohei Taniguchi, MD, PhD Takashi Nuri, MD, PhD SangWoong Lee, MD, PhD Koichi Ueda, MD, PhD Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b Plastic and Reconstructive Surgery, Global Open |
| title | Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b |
| title_full | Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b |
| title_fullStr | Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b |
| title_full_unstemmed | Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b |
| title_short | Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b |
| title_sort | experimental study of warburg effect in keloid nodules implication for downregulation of mir 133b |
| url | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000005202 |
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