2. Academic Validation
  3. Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway

Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway

  • BMC Ophthalmol. 2023 Jul 6;23(1):302. doi: 10.1186/s12886-023-03046-5.
Chaojun Fu 1 2,  Jun Peng 3,  Yanjun Ling 4,  Hongqing Zhao 1,  Yongwang Zhao 5,  Xiuli Zhang 1,  Min Ai 1 2,  Qinghua Peng 6 7,  Yuhui Qin 8 9
Affiliations

Affiliations

  • 1 Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases With Chinese Medicine, Hunan University of Chinese Medicine, Hanpu Rd., Yuelu District, Changsha, 410208, Hunan, China.
  • 2 Hunan Engineering Technological Research Center for the Prevention and Treatment of Otolaryngologic Disease and Protection of Visual Function With Chinese Medicine, Changsha, 410208, Hunan, China.
  • 3 Ophthalmology Department, The First Hospital of Hunan University of Chinese Medicine, Shaoshan Rd., Yuhua District, Changsha, 410007, Hunan, China.
  • 4 Institute of Chinese Medicine of Hunan Province, Lushan Rd., Yuelu District, Changsha, 410006, Hunan, China.
  • 5 Ophthalmology Department, Songjiang Branch of the First People's Hospital affiliated to Shanghai Jiao Tong University, Zhongshan Zhong Rd., Songjiang District, Shanghai, 201699, China.
  • 6 Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases With Chinese Medicine, Hunan University of Chinese Medicine, Hanpu Rd., Yuelu District, Changsha, 410208, Hunan, China. [email protected].
  • 7 Hunan Engineering Technological Research Center for the Prevention and Treatment of Otolaryngologic Disease and Protection of Visual Function With Chinese Medicine, Changsha, 410208, Hunan, China. [email protected].
  • 8 Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases With Chinese Medicine, Hunan University of Chinese Medicine, Hanpu Rd., Yuelu District, Changsha, 410208, Hunan, China. [email protected].
  • 9 Hunan Engineering Technological Research Center for the Prevention and Treatment of Otolaryngologic Disease and Protection of Visual Function With Chinese Medicine, Changsha, 410208, Hunan, China. [email protected].
PMID: 37415101 DOI: 10.1186/s12886-023-03046-5
Abstract

Background: Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism.

Methods: Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/Akt Inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/Akt pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay.

Results: HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/Akt pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/Akt pathway.

Conclusions: Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/Akt pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.

Keywords

Angiogenesis; Apigenin; Diabetic retinopathy; PTEN/PI3K/AKT; miR-140-5p/HDAC3.

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