Long non-coding RNA H19 knockout activates the SAHH/DNMT3b pathway and represses NLRP3 inflammasome expression in a diabetic rat model
- 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou 510060, Guangdong Province, China
Abstract
AIM: To explore the regulatory effect of long non-coding RNA H19 on the Nod-like receptor protein 3 (NLRP3) inflammasome and its functional role in the progression of diabetic retinopathy (DR). METHODS: Wild-type and H19 knockout rats were subjected to a high-fat and high-sugar diet combined with streptozotocin injection to establish an in vivo diabetes mellitus (DM) model. In vitro, rat primary retinal microvascular endothelial (CP-R114) cells were cultured under high-glucose conditions to mimic the diabetic microenvironment. The MTS assay was performed to evaluate cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of indicators related to glucose metabolism, lipid metabolism, oxidative stress, and inflammation in rat retinal tissues and CP-R114 cells. Hematoxylin and eosin (HE) staining was applied to observe the pathological morphological changes in retinal tissues. qRT-PCR was conducted to quantify the mRNA expression of H19, S-adenosylhomocysteine hydrolase (SAHH), and S-adenosylmethionine-dependent methyltransferase 3 beta (DNMT3b) in rat retinas. Western blotting and immunofluorescence staining were further utilized to detect the protein expression of SAHH, DNMT3b, NLRP3, Caspase-1, and interleukin (IL)-1β in retinal tissues. RESULTS: In DM model rats, H19 knockout significantly improved glucose and lipid metabolic disorders and alleviated oxidative stress. Notably, H19 deficiency effectively ameliorated retinal tissue injury. The expression levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and pro-inflammatory factors were markedly downregulated in H19-silenced DM rats. Mechanistically, H19 knockout upregulated the expression of SAHH and DNMT3b, while inhibiting the expression of NLRP3 inflammasome-associated proteins in DM rats. Consistent with the in vivo findings, H19 silencing suppressed NLRP3 inflammasome activation and elevated SAHH and DNMT3b expression in high-glucose-stimulated CP-R114 cells. CONCLUSION: This study demonstrates that H19 knockout alleviates DR progression in diabetic rats by activating the SAHH/DNMT3b signaling pathway and inhibiting NLRP3 inflammasome activation. Therefore, targeting H19 represents a promising novel therapeutic strategy for the clinical treatment of DR.
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BibTeX
@article{chen2026long,
title = {{Long non-coding RNA H19 knockout activates the SAHH/DNMT3b pathway and represses NLRP3 inflammasome expression in a diabetic rat model}},
author = {Hui Chen and Yu-Hui Pang and Xiong-Ze Zhang and Nan-Ying Liao and Miao-Ling Li and Yu-Ying Ji and Lan Mi and Yu-Hong Gan and Yong-Yue Su and Feng Wen},
journal = {International Journal of Ophthalmology},
year = {2026},
month = nov,
doi = {10.18240/ijo.2026.11.04},
url = {https://doi.org/10.18240/ijo.2026.11.04},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Long non-coding RNA H19 knockout activates the SAHH/DNMT3b pathway and represses NLRP3 inflammasome expression in a diabetic rat model
AU - Hui Chen
AU - Yu-Hui Pang
AU - Xiong-Ze Zhang
AU - Nan-Ying Liao
AU - Miao-Ling Li
AU - Yu-Ying Ji
AU - Lan Mi
AU - Yu-Hong Gan
AU - Yong-Yue Su
AU - Feng Wen
PY - 2026
DA - 2026/11/02
JO - International Journal of Ophthalmology
DO - 10.18240/ijo.2026.11.04
UR - https://doi.org/10.18240/ijo.2026.11.04
AB - AIM: To explore the regulatory effect of long non-coding RNA H19 on the Nod-like receptor protein 3 (NLRP3) inflammasome and its functional role in the progression of diabetic retinopathy (DR). METHODS: Wild-type and H19 knockout rats were subjected to a high-fat and high-sugar diet combined with streptozotocin injection to establish an in vivo diabetes mellitus (DM) model. In vitro, rat primary retinal microvascular endothelial (CP-R114) cells were cultured under high-glucose conditions to mimic the diabetic microenvironment. The MTS assay was performed to evaluate cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of indicators related to glucose metabolism, lipid metabolism, oxidative stress, and inflammation in rat retinal tissues and CP-R114 cells. Hematoxylin and eosin (HE) staining was applied to observe the pathological morphological changes in retinal tissues. qRT-PCR was conducted to quantify the mRNA expression of H19, S-adenosylhomocysteine hydrolase (SAHH), and S-adenosylmethionine-dependent methyltransferase 3 beta (DNMT3b) in rat retinas. Western blotting and immunofluorescence staining were further utilized to detect the protein expression of SAHH, DNMT3b, NLRP3, Caspase-1, and interleukin (IL)-1β in retinal tissues. RESULTS: In DM model rats, H19 knockout significantly improved glucose and lipid metabolic disorders and alleviated oxidative stress. Notably, H19 deficiency effectively ameliorated retinal tissue injury. The expression levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and pro-inflammatory factors were markedly downregulated in H19-silenced DM rats. Mechanistically, H19 knockout upregulated the expression of SAHH and DNMT3b, while inhibiting the expression of NLRP3 inflammasome-associated proteins in DM rats. Consistent with the in vivo findings, H19 silencing suppressed NLRP3 inflammasome activation and elevated SAHH and DNMT3b expression in high-glucose-stimulated CP-R114 cells. CONCLUSION: This study demonstrates that H19 knockout alleviates DR progression in diabetic rats by activating the SAHH/DNMT3b signaling pathway and inhibiting NLRP3 inflammasome activation. Therefore, targeting H19 represents a promising novel therapeutic strategy for the clinical treatment of DR.
SN - 2222-3959
SN - 2227-4898
ER -