ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Kidney single-cell transcriptome profile reveals distinct response of proximal tubule cells to SGLT2i and ARB treatment in diabetic mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
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- Mitigation of renal tubular injury by SIRT6 may improve individual outcomes in diabetic kidney disease-potential mechanisms involving epigenetic repression of inflammatory responses.Journal of advanced research · 2026Article
- NDUFA5 deficiency promotes renal inflammation in diabetic nephropathy via mitochondrial ROS signaling.iScience · 2026Article
- Single-Cell Multimodal Profiling Highlights Persistent Aortic Smooth Muscle Cell Changes in Diabetic Mice Despite Glycemic Control.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Chronic Kidney Disease in Metabolic Disease: Regulation of SGLT2 and Transcriptomic-Epigenetic Effects of Its Pharmacological Inhibition.International journal of molecular sciences · 2026Review
- Azilsartan Ameliorates Diabetic Kidney Disease Through Modulation of Inflammation, Pyroptosis, and Mitochondrial Dysfunction.Journal of diabetes research · 2026Article
- Angiotensin receptor blocker ameliorates the development of tubulointerstitial injury and fibrosis associated with tubular proteinuria observed in subclinical diabetic kidney disease.Frontiers in pharmacology · 2026Article
- Germacrone Ameliorates Diabetic Kidney Disease by Activating TFEB to Promote Autophagy and Inhibit Inflammation.ACS omega · 2025Article
- Current trends in single-cell RNA sequencing applications in diabetes mellitus.FEBS open bio · 2025Review
- Canagliflozin Attenuates Podocyte Inflammatory Injury through Suppressing the TXNIP/NLRP3 Signaling Pathway in Diabetic Kidney Disease Mice.Inflammation · 2025Article
- Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells.Journal of translational medicine · 2025Article
- Cellular crosstalk in organotypic vasculature: mechanisms of diabetic cardiorenal complications and SGLT2i responses.Cardiovascular diabetology · 2025Article
- Single-cell atlas reveals multi-faced responses of losartan on tubular mitochondria in diabetic kidney disease.Journal of translational medicine · 2025Article
- Application and Progression of Single-Cell RNA Sequencing in Diabetes Mellitus and Diabetes Complications.Journal of diabetes research · 2025Review
- Transcriptomics of SGLT2-positive early proximal tubule segments in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism.American journal of physiology. Renal physiology · 2025Article
- HFD-induced Alterations in Renal Tubular Oatp4c1-P-gp Transport Systems in Mice: Impact on Digoxin Renal Excretion and Gadolinium-Enhanced Radiological Manifestations.Current drug metabolism · 2025Article
- Single-cell RNA sequencing in diabetic kidney disease: a literature review.Renal failure · 2024Review
- The advance of single cell transcriptome to study kidney immune cells in diabetic kidney disease.BMC nephrology · 2024Review
- State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications.American journal of hypertension · 2024Review
- How can inhibition of glucose and sodium transport in the early proximal tubule protect the cardiorenal system?Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been used as the standard therapy for patients with diabetic kidney disease (DKD). However, how these two drugs possess additive renoprotective effects remains unclear. Here, we conducted single-cell RNA sequencing to profile the kidney cell transcriptome of db/db mice treated with vehicle, ARBs, SGLT2i, or ARBs plus SGLT2i, using db/m mice as control. We identified 10 distinct clusters of kidney cells with predominant proximal tubular (PT) cells. We found that ARBs had more anti-inflammatory and anti-fibrotic effects, while SGLT2i affected more mitochondrial function in PT. We also identified a new PT subcluster, was increased in DKD, but reversed by the treatments. This new subcluster was also confirmed by immunostaining of mouse and human kidneys with DKD. Together, our study reveals kidney cell-specific gene signatures in response to ARBs and SGLT2i and identifies a new PT subcluster, which provides new insight into the pathogenesis of DKD.
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