Early renal structural changes and potential biomarkers in diabetic nephropathy

Líu, Hao; Jiang, Feng; Tang, Liling

doi:10.3389/fphys.2022.1020443

Cited by 24 publications

(20 citation statements)

References 71 publications

(69 reference statements)

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“…Recent studies have showed that glomerular injury markers SMAD1 and Podocalyxin were strongly associated with the severity of expansion of the mesangial matrix. And the tubular injury markers Netrin-1, L-FABP, and NGAL were signi cantly higher in diabetic patients than in controls [32] . In addition, lots of microRNAs and lncRNAs were also considered as biomarkers in early diagnosis and treatment of DN [33,34] .…”

Section: Discussionmentioning

confidence: 84%

Microarray expression profile of exosomal circRNAs from high glucose stimulated human renal tubular epithelial cells

Sha

Lai

Zhang

et al. 2023

Preprint

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Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic nephropathy (DN) for their stability and enrichment in exosomes. However, the role of circRNAs from exosome of tubular epithelial cells in DN development has not been fully illustrated. In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. We found the exosome concentration was higher in HG stimulated HK-2 cells compared with controls. 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of HG group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis indicated that circRNA parental genes were associated with glucose metabolism, lipid metabolism and inflammatory process, which are important in DN development. Further analysis of circRNA/miRNA interaction indicated that some differentially expressed circRNAs interacted with one or more binding sites of miRNAs, which are associated with diabetes or DN. In conclusion, our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers and play a critical role in the progression of DN.

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Section: Discussionmentioning

confidence: 84%

Microarray expression profile of exosomal circRNAs from high glucose stimulated human renal tubular epithelial cells

Sha

Lai

Zhang

et al. 2023

Preprint

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“…This nding is signi cant because uL-FABP increase is a typical expression of tubular damage that is probably one of the rst histologically relevant signs in DN pathophysiology. Subsequently, after the rst damage step, the pathophysiological course of DN most often switches to glomerular involvement and impaired barrier function with albuminuria, overt proteinuria, increased serum creatinine levels, and reduced GFR [45]. Therefore, the fact that this tubular damage marker was demonstrated to be able to predict the onset and progression of glomerular involvement is important and indicates that uL-FABP can detect renal impairment progression in microalbuminuric T2DM patients and that its diagnostic power is also relevant in advanced DN stages as a predictor of disease progression over time [28].…”

Section: Discussionmentioning

confidence: 99%

Urinary L-FABP: a potential novel early biomarker for Diabetic Nephropathy? A systematic review of the literature

Satta¹,

Strollo

Borgia

et al. 2023

Preprint

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Introduction: Patients with Type 1 and Type 2 diabetes mellitus (T1DM and T2DM) are at high risk of developing chronic kidney disease (CKD), i.e., diabetic nephropathy (DN), whose onset and progression are associated with a high morbidity and mortality risk. Early DN prediction is crucial. Presently it relies on albumin excretion rate (AER) and glomerular filtration rate (GFR) assessment. Nevertheless, recent literature reports that DN eventually affects patients with normal AER and GFR values. Therefore, further cost-effective biomarkers of DN onset or fast worsening are needed. Intracellular liver-type fatty acid-binding protein (L-FABP) has been associated with renal tubular-interstitial damage and could help predict and diagnose DN. Methods: we performed a systematic review of the literature to evaluate the performance of urinary excretion of such biomarker (uL-FABP) in predicting and diagnosing DN and its progression in T2DM and T1DM patients. To do so, we evaluated 635 publications on four major scientific databases, 21 of which were suited for inclusion in this review. Results: we selected twenty-one in-extenso publications, 14 reporting a cross-sectional design/arm (nine on T2DM, four on T1DM, and one on both). Ten included a longitudinal design/arm. Cross-sectional studies, primarily conducted in Asian and north-European populations, showed uL-FABP levels to correlate directly with DN severity (micro-, macro-albuminuria, and overt CKD) in T1DM and T2DM, besides being significantly higher than in healthy controls in the case of normoalbuminuria. In addition, longitudinal ones showed baseline uL-FABP to predict DN onset in normoalbuminuric patients with T1DM and DN progression independently of diabetes type. Discussion: the studies analyzed in this review suggest that uL-FABP is a marker of tubular damage detectable before increased albumin excretion and can represent the earliest sign of kidney dysfunction in diabetes. Indeed, it discloses DN onset and often predicts DN severity from start to end-stage renal disease (ESRD) in T2DM and T1DM patients. Currently, uL-FABP can be assessed on a routine basis and, being available as a point-of-care fast test kit, may also become an easy-to-handle diagnostic tool for outpatients. Conclusions: uL-FABP represents a cost-effective and user-friendly biomarker of DN and can even predict DN progression in T2DM and T1DM over time.

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“…Various pathophysiological mechanisms have been supposed in DN development including hyperglycemia, inflammation, oxidative stress, advanced glycation end products, protein kinase C, and poly(ADP-ribose) polymerase activation [ 11 , 12 , 13 ] ( Figure 1 ). Taken together, these factors are responsible for the morphological impairments occurring at renal site in DN, such as glomerular mesangium hypertrophy, podocytes dysfunction, and extracellular matrix proteins accumulation [ 13 , 14 ]. From a molecular perspective, different cellular and inflammatory signaling pathways such as transforming growth factor- β (TGF- β ), Phosphoinositide 3-kinase-protein kinase B (PI3K-Akt), Mitogen-activated protein kinase (MAPK) family including P38, extracellular signal-regulated kinases (ERK), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B), and c-Jun N-terminal kinases (JNKs) have been implied in DN pathogenesis [ 13 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Besides classical markers (e.g., urinary cystatin C) [ 10 , 19 , 20 , 21 ], novel promising options are emerging in this research area [ 14 , 20 , 22 ]. In this framework, a pathogenic role for microRNAs (miRNAs) as biomolecules regulating up to 30% of the protein-coding genes in the human genome has been also proposed [ 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Pediatric Diabetic Nephropathy: Novel Insights from microRNAs

Lanzaro

Barlabà

Nigris

et al. 2023

JCM

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Diabetic nephropathy (DN) represents the most common microvascular complication in patients with diabetes. This progressive kidney disease has been recognized as the major cause of end-stage renal disease with higher morbidity and mortality. However, its tangled pathophysiology is still not fully known. Due to the serious health burden of DN, novel potential biomarkers have been proposed to improve early identification of the disease. In this complex landscape, several lines of evidence supported a critical role of microRNAs (miRNAs) in regulating posttranscriptional levels of protein-coding genes involved in DN pathophysiology. Indeed, intriguing data showed that deregulation of certain miRNAs (e.g., miRNAs 21, -25, -92, -210, -126, -216, and -377) were pathogenically linked to the onset and the progression of DN, suggesting not only a role as early biomarkers but also as potential therapeutic targets. To date, these regulatory biomolecules represent the most promising diagnostic and therapeutic options for DN in adult patients, while similar pediatric evidence is still limited. More, findings from these elegant studies, although promising, need to be deeper investigated in larger validation studies. In an attempt to provide a comprehensive pediatric overview in the field, we aimed to summarize the most recent evidence on the emerging role of miRNAs in pediatric DN pathophysiology.

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Early renal structural changes and potential biomarkers in diabetic nephropathy

Cited by 24 publications

References 71 publications

Microarray expression profile of exosomal circRNAs from high glucose stimulated human renal tubular epithelial cells

Microarray expression profile of exosomal circRNAs from high glucose stimulated human renal tubular epithelial cells

Urinary L-FABP: a potential novel early biomarker for Diabetic Nephropathy? A systematic review of the literature

Pediatric Diabetic Nephropathy: Novel Insights from microRNAs

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