The role of discoid domain receptor 1 on renal tubular epithelial pyroptosis in diabetic nephropathy

• 영문명: The role of discoid domain receptor 1 on renal tubular epithelial pyroptosis in diabetic nephropathy
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Weichen Zhao Chunyuan He Junjie Jiang Zongbiao Zhao Hongzhong Yuan Facai Wang Bingxiang Shen
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제26권 제6호, 427~438쪽, 전체 12쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2022.11.30

영문 초록

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

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INTRODUCTION

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키워드

Diabetic nephropathy Discoid domain receptor 1 NLR family pyrin domain-containing 3 Nuclear factor kappa B Pyroptosis