ArticleScientific reports2016
C-Reactive Protein Promotes Diabetic Kidney Disease in db/db Mice via the CD32b-Smad3-mTOR signaling Pathway.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 66 citations in OpenAlex.
- Stage-wise variation in serum C-reactive protein and cardiovascular risk in chronic kidney disease of uncertain etiology among Sri Lankans; a preliminary study.BMC research notes · 2026Article
- Hepatokines and polycystic ovary syndrome: investigating the connection between the hepato-ovarian axis and disorders in glycolipid metabolism in PCOS: a narrative review.Frontiers in endocrinology · 2026Review
- Monomeric C-reactive Protein Exacerbates Neuronal Injury and Enhances Microglial Activation after Global Cerebral Ischemia in Mice.Molecular neurobiology · 2025Article
- Serum C-reactive protein and C-reactive protein derived markers in diabetic microvascular complications.World journal of diabetes · 2025Review
- Monomeric [CRP] and CRP-Controlled Stress and Pain Hypersensitization as Novel Predictors of Cognitive Disturbance and AD in Chronic Inflammatory Disease.International journal of molecular sciences · 2025Review
- P16-positive senescent cells promote DKD by the dysregulation of glycolysis and mitochondrial metabolism.Cell death discovery · 2025Article
- Effectiveness and safety of Tongxinluo capsule for diabetic kidney disease: A systematic review and meta-analysis.World journal of diabetes · 2025Article
- The risk factors for cardiovascular disease and chronic kidney disease in patients with nonalcoholic fatty liver disease in Saudi Arabia.Saudi medical journal · 2025Article
- Article
- C-reactive protein in diabetic kidney disease: A new therapeutic avenue?Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- C-reactive protein promotes diabetic kidney disease via Smad3-mediated NLRP3 inflammasome activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Stroke-Induced Renal Dysfunction: Underlying Mechanisms and Challenges of the Brain-Kidney Axis.CNS neuroscience & therapeutics · 2024Review
- TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).Molecular medicine reports · 2024Review
- Renal macrophages and NLRP3 inflammasomes in kidney diseases and therapeutics.Cell death discovery · 2024Review
- Senolytic combination of dasatinib and quercetin protects against diabetic kidney disease by activating autophagy to alleviate podocyte dedifferentiation via the Notch pathway.International journal of molecular medicine · 2024Article
- Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.International journal of biological sciences · 2024Article
- Mendelian randomization analysis reveals causal factors behind diabetic nephropathy: evidence, opportunities, and challenges.Frontiers in endocrinology · 2024Review
- [The Role of TGF-β1/SMAD in Diabetic Nephropathy: Mechanisms and Research Development].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- Effect of Prunetin on Streptozotocin-Induced Diabetic Nephropathy in Rats - a Biochemical and Molecular Approach.Biomolecules & therapeutics · 2023Article
- The Potential Role of C-Reactive Protein in Metabolic-Dysfunction-Associated Fatty Liver Disease and Aging.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C-reactive protein (CRP) is associated with progressive diabetic nephropathy in patients with type-2 diabetes (T2DN). However, role of CRP in T2DN remains unclear. We report here that CRP is pathogenic in T2DN in db/db mice that express human CRP (CRPtg-db/db). Compared to the littermate db/db mice, CRPtg-db/db developed more severe T2DN, showing higher levels of fasting blood glucose and microalbuminuria and more progressive renal inflammation and fibrosis. Enhanced T2DN in CRPtg-db/db mice were associated with over-activation of CRP-CD32b, NF-κB, TGF-β/Smad3, and mTOR signaling. Further studies in vitro defined that CRP activated Smad3 directly at 15 mins via the CD32b- ERK/p38 MAP kinase crosstalk pathway and indirectly at 24 hours through a TGF-β1-dependent mechanism. Importantly, CRP also activated mTOR signaling at 30 mins via a Smad3-dependent mechanism as Smad3 bound mTOR physically and CRP-induced mTOR signaling was abolished by a neutralizing CD32b antibody and a specific Smad3 inhibitor. Finally, we also found that CRP induced renal fibrosis through a CD32b-Smad3-mTOR pathway because blocking mTOR signaling with rapamycin inhibited CRP-induced CTGF and collagen I expression. Thus, CRP is pathogenic in T2DN. CRP may promote CD32b- NF-κB signaling to mediate renal inflammation; whereas, CRP may enhance renal fibrosis in T2DN via CD32b-Smad3-mTOR signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.