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pmid:40751815

Revealing the regulatory role of lncRNAs SNHG1 and CRNDE on Th17/Treg imbalance in diabetic kidney disease.

Seyed Amirhossein Hosseini · Parisa Ajorlou · Pegah Mousavi · Mohammad Shekari

Clinical and experimental medicine · 2025 doi:10.1007/s10238-025-01802-z

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complete

Experiment

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Data

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absent

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title
Revealing the regulatory role of lncRNAs SNHG1 and CRNDE on Th17/Treg imbalance in diabetic kidney disease.
doi
10.1007/s10238-025-01802-z
pmid
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Seyed Amirhossein Hosseini
[1]
Parisa Ajorlou
[2]
Pegah Mousavi
[3]
Mohammad Shekari
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Clinical and experimental medicine
year
2025
abstract
Diabetic kidney disease (DKD) is a chronic inflammatory condition associated with diabetes that can progress to end-stage renal disease (ESRD). However, our knowledge about the epigenetic regulatory mechanism underlying the imbalance of Th17/Treg cells in inflammatory responses remains unclear. Therefore, our aim in this study was to identify regulatory lncRNAs involved in differentiating Th17/Treg cell lines. Regulatory lncRNAs associated with DKD were identified by analyzing the GSE43005 and GSE142025 datasets from the GEO database and conducting a comprehensive literature review. After identifying differentially expressed genes (DEGs), we validated our bioinformatics results using real-time PCR. In our study, ninety individuals were recruited and assigned to four groups: 30 with Type 2 Diabetes (T2D), 15 with early-stage DKD (microalbuminuria), 15 with advanced DKD (ESRD), and 30 healthy controls. The correlation between target genes and clinical laboratory findings, such as BUN, creatinine, ESR, GFR, urea, FBS, HbA1C, and 2hpp was assessed. The results indicated that CRNDE, which positively affects the expression of RORC and IL-17 genes, was upregulated in individuals with ESRD and T2D. Conversely, in the Treg cell line, SNHG1, a positive regulator of FOXP3, was significantly downregulated in ESRD, microalbuminuria, and T2D patients. Interestingly, TGF-β cytokine expression was increased in ESRD and microalbuminuria patients. Our findings suggest that SNHG1 and CRNDE may contribute to the regulation of Th17/Treg imbalance and the progression of inflammatory responses in DKD. These genes may serve as novel biomarkers for the diagnosis and prognosis of DKD. Further research into the effects of anti-inflammatory drugs on modulating immune system responses is a critical step toward mitigating kidney damage.
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Differentially expressed genes (DEGs) were identified using GEO2R, applying thresholds of |log₂ fold change (FC)|> 1 and an adj. p-value < 0.05 [21]. One-way ANOVA was applied to analyze data with a normal distribution, whereas the Kruskal Wallis test was employed for non-normally distributed data.
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sections[3] "Identification of lncRNAs regulating Th17 and Treg cell differentiation" paragraph 3
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Differentially expressed genes (DEGs) were identified using GEO2R, applying thresholds of |log₂ fold change (FC)|> 1 and an adj. p-value < 0.05 [21].
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One-way ANOVA was applied to analyze data with a normal distribution, whereas the Kruskal Wallis test was employed for non-normally distributed data.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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CRNDE expression was increased in patients with T2D and ESRD, whereas SNHG1 expression was decreased in patients with T2D, microalbuminuria, and ESRD.
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The results indicated that CRNDE, which positively affects the expression of RORC and IL-17 genes, was upregulated in individuals with ESRD and T2D. Conversely, in the Treg cell line, SNHG1, a positive regulator of FOXP3, was significantly downregulated in ESRD, microalbuminuria, and T2D patients.
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sections[12] "Expression results" paragraph 2
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In addition, the expression of SNHG1 in subjects with T2D, microalbuminuria, and ESRD significantly decreased over time and with disease progression compared to healthy subjects (p = 0.0495, log2 FC = − 1.84; p = 0.0265, log2 FC = -2.31; p = 0.0007, log2 FC = − 3.36) (Fig. 3A).
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sections[12] "Expression results" paragraph 4
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Lastly, a significant increase in CRNDE expression was observed in individuals with T2D compared to the control group (p = 0.0248, log2 FC = 2.59), as well as in individuals with ESRD relative to healthy controls (p = 0.0009, log2 FC = 4.03) (Fig. 3B).
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However, our knowledge about the epigenetic regulatory mechanism underlying the imbalance of Th17/Treg cells in inflammatory responses remains unclear. Therefore, our aim in this study was to identify regulatory lncRNAs involved in differentiating Th17/Treg cell lines. Regulatory lncRNAs associated with DKD were identified by analyzing the GSE43005 and GSE142025 datasets from the GEO database and conducting a comprehensive literature review. After identifying differentially expressed genes (DEGs), we validated our bioinformatics results using real-time PCR. In our study, ninety individuals were recruited and assigned to four groups: 30 with Type 2 Diabetes (T2D), 15 with early-stage DKD (microalbuminuria), 15 with advanced DKD (ESRD), and 30 healthy controls. The correlation between target genes and clinical laboratory findings, such as BUN, creatinine, ESR, GFR, urea, FBS, HbA1C, and 2hpp was assessed. The results indicated that CRNDE, which positively affects the expression of RORC and IL-17 genes, was upregulated in individuals with ESRD and T2D. Conversely, in the Treg cell line, SNHG1, a positive regulator of FOXP3, was significantly downregulated in ESRD, microalbuminuria, and T2D patients. Interestingly, TGF-β cytokine expression was increased in ESRD and microalbuminuria patients. Our findings suggest that SNHG1 and CRNDE may contribute to the regulation of Th17/Treg imbalance and the progression of inflammatory responses in DKD. These genes may serve as novel biomarkers for the diagnosis and prognosis of DKD. Further research into the effects of anti-inflammatory drugs on modulating immune system responses is a critical step toward mitigating kidney damage.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using GEO2R, applying thresholds of |log₂ fold change (FC)|> 1 and an adj. p-value < 0.05 [21]. One-way ANOVA was applied to analyze data with a normal distribution, whereas the Kruskal Wallis test was employed for non-normally distributed data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40751815", "locator": "sections[3] \"Identification of lncRNAs regulating Th17 and Treg cell differentiation\" paragraph 3", "quote": "Differentially expressed genes (DEGs) were identified using GEO2R, applying thresholds of |log₂ fold change (FC)|> 1 and an adj. p-value < 0.05 [21]."}, {"asset": "source:pmid:40751815", "locator": "sections[7] \"Statistical analysis\" paragraph 2", "quote": "One-way ANOVA was applied to analyze data with a normal distribution, whereas the Kruskal Wallis test was employed for non-normally distributed data."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40751815", "locator": "sections[22] \"Data availability\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CRNDE expression was increased in patients with T2D and ESRD, whereas SNHG1 expression was decreased in patients with T2D, microalbuminuria, and ESRD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40751815", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The results indicated that CRNDE, which positively affects the expression of RORC and IL-17 genes, was upregulated in individuals with ESRD and T2D. Conversely, in the Treg cell line, SNHG1, a positive regulator of FOXP3, was significantly downregulated in ESRD, microalbuminuria, and T2D patients."}, {"asset": "source:pmid:40751815", "locator": "sections[12] \"Expression results\" paragraph 2", "quote": "In addition, the expression of SNHG1 in subjects with T2D, microalbuminuria, and ESRD significantly decreased over time and with disease progression compared to healthy subjects (p = 0.0495, log2 FC = − 1.84; p = 0.0265, log2 FC = -2.31; p = 0.0007, log2 FC = − 3.36) (Fig. 3A)."}, {"asset": "source:pmid:40751815", "locator": "sections[12] \"Expression results\" paragraph 4", "quote": "Lastly, a significant increase in CRNDE expression was observed in individuals with T2D compared to the control group (p = 0.0248, log2 FC = 2.59), as well as in individuals with ESRD relative to healthy controls (p = 0.0009, log2 FC = 4.03) (Fig. 3B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CRNDE expression was increased in patients with T2D and ESRD, whereas SNHG1 expression was decreased in patients with T2D, microalbuminuria, and ESRD.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40751815"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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