Sharma VK, Beg MMA, Singh S, Singh SK, Shrivastav D. SLC30A8 (ZnT8) at the crossroads of epigenetics and microRNA regulation in type 2 diabetes and nephropathy. World J Nephrol 2026; 15(3): 122565 [DOI: 10.5527/wjn.122565]
Corresponding Author of This Article
Dharmsheel Shrivastav, PhD, Assistant Professor, Department of Biotechnology, Microbiology and Forensic Sciences, School of Sciences, Noida International University, Plot 1, Yamuna Expy, Sector 17A, Greater Noida 203201, Uttar Pradesh, India. dharmsheel.shrivastav1@gmail.com
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Biochemistry & Molecular Biology
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review-article
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Sharma VK, Beg MMA, Singh S, Singh SK, Shrivastav D. SLC30A8 (ZnT8) at the crossroads of epigenetics and microRNA regulation in type 2 diabetes and nephropathy. World J Nephrol 2026; 15(3): 122565 [DOI: 10.5527/wjn.122565]
Varun Kumar Sharma, Shilpy Singh, Dharmsheel Shrivastav, Department of Biotechnology, Microbiology and Forensic Sciences, School of Sciences, Noida International University, Greater Noida 203201, Uttar Pradesh, India
Mirza Masroor Ali Beg, Faculty of Medicine, Ala-Too International University, Bishkek 720048, Kyrgyzstan
Sourabh Kumar Singh, Department of Forensic Science, School of Basic and Applied Sciences, K.R. Mangalam University, Gurugram 122103, India
Author contributions: All authors contributed to the study design; conception and Content collection were performed by Shrivastav D, Beg MMA and Sharma VK; the first draft of the manuscript was written by Shrivastav D, Beg MMA, Singh SK and Sharma VK commented on previous versions of the manuscript; final review and editing of the manuscript were done by Shrivastav D, Singh SK, and Sharma VK; all authors read and approved the final manuscript.
AI contribution statement: The authors take full responsibility and accountability for all content of this manuscript, including any portions for which AI tools were used as assistive technologies. All AI-assisted outputs were carefully reviewed, validated, and approved by the authors. AI tools were not used to generate original scientific data, perform independent scientific analyses, or draw scientific conclusions.
Supported by Intramural Seed Money Grant (Project ID NS. 9) from Noida International University, Gautam Budh Nagar, Uttar Pradesh, India, No. NIU/ODR1/2026/IMR/25.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Dharmsheel Shrivastav, PhD, Assistant Professor, Department of Biotechnology, Microbiology and Forensic Sciences, School of Sciences, Noida International University, Plot 1, Yamuna Expy, Sector 17A, Greater Noida 203201, Uttar Pradesh, India. dharmsheel.shrivastav1@gmail.com
Received: April 22, 2026 Revised: June 10, 2026 Accepted: July 9, 2026 Published online: September 25, 2026 Processing time: 113 Days and 15.3 Hours
Abstract
Diabetic nephropathy (DN) is a major kidney disease and linked to type 2 diabetes mellitus (T2DM), and it significantly which increases the global health burden. In the pathogenesis of DN, ZnT8 is essential for zinc transport into insulin granules; it ensures proper insulin crystallization, storage, and secretion while safeguarding β-cells against oxidative stress. it is suggested that the in pathogenesis of DN, the role of the SLC30A8/ZnT8/PDX-1 axis is underexplored along with its mechanism linking β-cell impairment to T2DM progression and renal fibrosis. In this review, we explore the role of microRNA-mediated regulation of SLC30A8/ZnT8 via PDX-1. Under hyperglycaemic and glucolipotoxic conditions, elevated level of miR-375 and miR-765 suppresses PDX-1 (master regulator of β-cell identity) and transcription of SLC30A8, culminating in ZnT8 silencing. PDX-1 directly binds to SLC30A8 enhancers and modulates its expression. Therapeutic targeting of this pathway via miR-375 and miR-765 antagomirs, CRISPR editing, ZnT8 overexpression, or zinc supplementation offers promise for restoring β-cell function and mitigating DN. Large scale clinical trial and epigenetic studies on patient cohorts will help and guide precision interventions.
Core Tip: Diabetic nephropathy is a major complication of type 2 diabetes mellitus. This review highlights the emerging role of the miR-375/miR-765–PDX-1–SLC30A8/ZnT8 regulatory axis in β-cell dysfunction and renal injury. Targeting this pathway through epigenetic and gene-based therapies may restore insulin homeostasis and offer novel strategies for diabetic nephropathy management.
