Upregulation of Fibroblast Growth Factors Caused by Heart and Neural Crest Derivatives Expressed 2 Suppression in Endometriotic Cells: A Possible Therapeutic Target in Endometriosis

Nao Kato, Kato N, Akira Iwase, Iwase A, Ishida C, Chiharu Ishida, Nagai T, Takashi Nagai, Mori M, Masahiko Mori, Bayasula, Nakamura T, Tomoko Nakamura, Satoko Osuka, Osuka S, Umida Ganiyeva, Ganiyeva U, Ying Qin, Qin Y, Rika Miki, Fumitaka Kikkawa, Miki R, Kikkawa F
Reproductive sciences (Thousand Oaks, Calif.) · 2019 · doi:10.1177/1933719118802053 · PMID:30270745
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⚙ AI-generated summary by claude@2026-06, 2026-06-12 ⓘ

Reduced HAND2 expression in endometriotic cells upregulates FGF1, FGF2, and FGF9, enhancing their migration and invasion, with FGF receptor inhibitors showing therapeutic potential.

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This doctoral thesis investigates how HAND2 (heart and neural crest derivatives expressed 2) affects the expression of fibroblast growth factors in endometriotic cells, focusing on whether HAND2 suppression leads to fibroblast growth factor upregulation. Using endometriotic cell models, the study reports that suppression of HAND2 is associated with increased fibroblast growth factor (FGF) levels, and it frames this pathway as a potential therapeutic target in endometriosis. A key limitation explicitly reflected in the thesis context is that the work is conducted at the cellular/experimental level rather than demonstrating clinical efficacy. This paper is centrally about endometriosis — it analyzes the HAND2→FGF upregulation mechanism in endometriotic cells as a candidate target for endometriosis treatment.

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Abstract

Several features exist that distinguish endometriotic cells from eutopic endometrial cells. Progesterone resistance is one of the main distinguishing features, although how progesterone resistance affects the phenotype of endometriotic cells is not fully elucidated. Heart and neural crest derivatives expressed 2 (HAND2) is a transcriptional factor that plays an important role in maintaining endometrial function in a progesterone-dependent manner. Therefore, we explored whether progesterone-dependent HAND2 is implicated in the progression of endometriosis. HAND2 was less expressed by endometriotic tissues compared to endometrial tissues. Suppression of HAND2 expression induced fibroblast growth factor 1 (FGF1), FGF2, and FGF9 in endometriotic stromal cells and consequently enhanced migration and invasion capacity. AZD4547, a FGF receptor inhibitor, diminished the migration and invasion of endometriotic cells in vitro. In the murine model of endometriosis, AZD4547 showed suppressive effects on the development of endometriotic lesions at a relatively low concentration. In conclusion, we demonstrated that FGF1, FGF2, and FGF9 are downstream effectors of HAND2 in endometriotic cells. Since HAND2-dependent FGFs play roles in enhancing invasive capacity of endometriotic cells, our results suggest that FGF receptor inhibitors, such as AZD4547, can be promising therapeutic targets for endometriosis.
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WEKO3 アイテム Upregulation of Fibroblast Growth Factors Caused by Heart and Neural Crest Derivatives Expressed 2 Suppression in Endometriotic Cells: A Possible Therapeutic Target in Endometriosis http://hdl.handle.net/2237/00029209 http://hdl.handle.net/2237/00029209448541fa-2405-474f-bb4e-2da128001cb3 | 名前 / ファイル | ライセンス | アクション | |---|---|---| | k12544_abstract (842.7 kB) | | | | k12544_publication_list (114.4 kB) | | | | k12544_review (829.9 kB) | | | | k12544_thesis (1.1 MB) | | | アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | ||||| |---|---|---|---|---|---|---| | 公開日 | 2019-01-11 | ||||| | タイトル | |||||| | タイトル | Upregulation of Fibroblast Growth Factors Caused by Heart and Neural Crest Derivatives Expressed 2 Suppression in Endometriotic Cells: A Possible Therapeutic Target in Endometriosis | ||||| | 言語 | en | ||||| | その他のタイトル | |||||| | その他のタイトル | 子宮内膜症細胞におけるHAND2抑制によるFGFs亢進を標的とした子宮内膜症治療の可能性 | ||||| | 言語 | ja | ||||| | 著者 | Kato, Nao × Kato, Nao× 加藤, 奈緒 | ||||| | アクセス権 | |||||| | アクセス権 | open access | ||||| | アクセス権URI | http://purl.org/coar/access_right/c_abf2 | ||||| | 言語 | |||||| | 言語 | eng | ||||| | 資源タイプ | |||||| | 資源 | http://purl.org/coar/resource_type/c_db06 | ||||| | タイプ | doctoral thesis | ||||| | 書誌情報 | 発行日 2018-12-28 | ||||| | 学位名 | |||||| | 学位名 | 博士(医学) | ||||| | 言語 | ja | ||||| | 学位授与機関 | |||||| | 学位授与機関識別子Scheme | kakenhi | ||||| | 学位授与機関識別子 | 13901 | ||||| | 学位授与機関名 | 名古屋大学 | ||||| | 言語 | ja | ||||| | 学位授与機関名 | Nagoya University | ||||| | 言語 | en | ||||| | 学位授与年度 | |||||| | 学位授与年度 | 2018 | ||||| | 学位授与年月日 | |||||| | 学位授与年月日 | 2018-12-28 | ||||| | 学位授与番号 | |||||| | 学位授与番号 | 甲第12544号 | ||||| | 著者版フラグ | |||||| | 値 | ETD |

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endometriosis

MeSH descriptors

Basic Helix-Loop-Helix Proteins Cell Movement Cell Movement Endometriosis Endometrium Fibroblast Growth Factors Fibroblasts Animals Basic Helix-Loop-Helix Proteins Basic Helix-Loop-Helix Proteins Benzamides Benzamides Cells, Cultured Disease Models, Animal Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium

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