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Updated: Aug 14, 2025
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Published on: November 27, 2013
Transient receptor potential channel 6 knockdown prevents high glucose-induced Müller cell pyroptosis
Mingming Ma1, Shuzhi Zhao1, Chenxin Li1
1Department of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, China.
Background:
Transient receptor potential channel 6 (TRPC6) is reported to be involved in the pathogenesis of diabetic complications, but its role in diabetic retinopathy (DR) remains unknown. The aim of our study was to determine the role and mechanism of TRPC6 in DR.
Methods:
High glucose was used to construct a DR cell model using rat retinal Müller cells (rMC-1). Intracellular Ca2+, reactive oxygen species (ROS) and cell pyroptosis were evaluated by flow cytometry. Protein levels of NLRP3, pro-caspase-1, active caspase-1, gasdermin D (GSDMD), GSDMD-N, TRPC6 and H3K27ac were detected by Western blot. mRNA levels of EP300 and TRPC6 were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Levels of IL-1β and IL-18 were estimated by enzyme linked immunosorbent assay (ELISA). The interaction between EP300 and TRPC6 was validated by a chromatin immunoprecipitation assay.
Results:
The knockdown of TRPC6 reduced inflammation and cell pyroptosis in HG induced rMC-1 cells, whereas overexpression of TRPC6 had the opposite effects. The inhibition of ROS and NLRP3 reversed TRPC6-mediated cell pyroptosis in the DR cell model. In addition, EP300 increased the expression of H3K27ac and TRPC6 to promote cell pyroptosis, which was suppressed by the knockdown of TRPC6.
Conclusions:
Our study revealed a novel EP300/H3K27ac/TRPC6 signaling pathway that may contribute to HG induced Müller cell pyroptosis. TRPC6 played a novel role in Müller cell pyroptosis triggered by HG, and may be a potential target for DR treatment in the future.
