Novel Aspects of Transforming Growth Factor-Beta in Diabetic Kidney Disease

Nephron ◽  
2002 ◽  
Vol 92 (1) ◽  
pp. 7-21 ◽  
Author(s):  
Ken-ichi Tsuchida ◽  
Brian Cronin ◽  
Kumar Sharma
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Diabetic Kidney ◽  
Growth Factor Beta

How to inhibit transforming growth factor beta safely in diabetic kidney disease

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Yuxin Yang ◽  
Kexin Shi ◽  
Devang M. Patel ◽  
Fang Liu ◽  
Tieqiao Wu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Diabetic Kidney ◽  
Growth Factor Beta

scholarly journals Initial Combination Empagliflozin and Linagliptin Improves Kidney Fibrotic Marker in Patients With Type 2 Diabetes: A Randomized Controlled Trial

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A416-A416
Author(s):  
Nattapol Sathavarodom ◽  
Thanaporn Putthanuparp ◽  
Verapon Pinphanichakarn
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Response To Therapy ◽  
Diabetic Kidney ◽  
Initial Combination

Abstract Background: Transforming growth factor-beta 1 (TGF- ß1) is a novel cytokine marker and also one of the therapeutic targets in the treatment of diabetic kidney disease. Both sodium glucose co-transporter 2 inhibitor and dipeptidyl-peptides 4 inhibitor reduce TGF- ß 1 level in animal studies, but whether it is effective in human is unknown. Objective: To evaluate the effects of combinations of empagliflozin/linagliptin, comparing with empagliflozin alone, in patients with type 2 diabetes. Material and Methods: Subjects are randomized to a combination of empagliflozin 10 mg and linagliptin 5 mg (n = 23), or empagliflozin 10 mg (n = 22) as add-on to standard treatment for 12 weeks. The primary end point is changed from baseline in serum TGF- ß1 at 12 weeks. Results: Among the 45 subjects who completed the study, mean change in TGF-ß1 was -928.2 + 1,204.2 pg/mL, and +206.6 + 592.5 pg/mL in the empagliflozin/linagliptin group and empagliflozin group, respectively (p <0.001). Mean change in estimated glomerular filtration rate (eGFR) increased in the empagliflozin /linagliptin group 4.4 + 7.59 mL/min/1.73m2, whereas mean eGFR decreased in empagliflozin group -0.06 + 11.16 mL/min/1.73m2 (p =0.133). Mean change in HbA1c was -1.3 + 0.6% and -0.4 + 0.6% in empagliflozin/linagliptin and empagliflozin group, respectively (p<0.001). Baseline level of eGFR significantly correlated with baseline TGF- ß1 but did not predict response to therapy. Conclusion: Initial combination empagliflozin and linagliptin may delay progression of kidney fibrosis as early as 12 weeks of treatment. Our study supports that this combination had synergistic action not only glycemic control but also beneficial in kidney protection. Keyword: transforming growth factor - ß1, diabetic kidney disease, combination empagliflozin and linagliptin

scholarly journals BKCa Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-β1/Smad2/3 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhigui Wu ◽  
Wenxian Yin ◽  
Mengqi Sun ◽  
Yuankai Si ◽  
Xiaoxiao Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Diabetic Kidney

Objective. To explore the role and mechanism of BKCa in diabetic kidney disease. Methods. Rat mesangial cells (MCs) HBZY-1 were cultured with high glucose to simulate the high-glucose environment of diabetic kidney disease in vivo. The effects of large conductance calcium-activated potassium channel (BKCa) on proliferation, migration, and apoptosis of HBZY-1 cells were observed. The contents of transforming growth factor beta 1 (TGF-β1), Smad2/3, collagen IV (Col IV), and fibronectin (FN) in the extracellular matrix were also observed. Results. High glucose significantly damaged HBZY-1 cells, which enhanced the ability of cell proliferation, migration, and apoptosis, and increased the secretion of Col IV and FN. Inhibition of BKCa and TGF-β1/Smad2/3 signaling pathways can inhibit the proliferation, migration, and apoptosis of HBZY-1 cells and suppress the secretion of Col IV and FN. The effect of excitation is the opposite. Conclusions. BKCa regulates mesangial cell proliferation, migration, apoptosis, and secretion of Col IV and FN and is associated with TGF-β1/Smad2/3 signaling pathway.

scholarly journals Diabetic Kidney Disease Alters the Transcriptome and Function of Human Adipose-Derived Mesenchymal Stromal Cells but Maintains Immunomodulatory and Paracrine Activities Important for Renal Repair

2021 ◽  
Author(s):  
LaTonya J. Hickson ◽  
Alfonso Eirin ◽  
Sabena M. Conley ◽  
Timucin Taner ◽  
Xiaohui Bian ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Stromal Cells ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Inflammatory Marker ◽  
Patient Characteristics ◽  
Rna Seq ◽  
Diabetic Kidney

<a>Mesenchymal stem/stromal cells (MSC) facilitate repair in experimental diabetic kidney disease (DKD). However, the hyperglycemic and uremic milieu may diminish regenerative capacity of patient-derived therapy. We hypothesized that DKD reduces human MSC paracrine function. Adipose-derived MSC from 38 DKD participants and 16 controls were assessed for cell surface markers, tri-lineage differentiation, RNA-sequencing (RNA-seq), <i>in vitro</i> function (co-culture or conditioned medium experiments with T cells and human kidney cells [HK-2]), secretome profile, and cellular senescence abundance. The direction of association between MSC function and patient characteristics were also tested. RNA-seq analysis identified 353 differentially expressed genes and downregulation of several immunomodulatory genes/pathways in DKD- <i>vs</i>. Control-MSC. DKD-MSC phenotype, differentiation, and tube formation capacity were preserved but migration was reduced. DKD-MSC with and without interferon-γ priming inhibited T-cell proliferation greater than Control-MSC. DKD-MSC-medium contained higher levels of anti-inflammatory cytokines (indoleamine 2,3-deoxygenase-1 and prostaglandin-E2) and pro-repair factors (hepatocyte growth factor and stromal cell-derived factor-1) but lower Interleukin-6 vs. Control-MSC-medium. DKD-MSC-medium protected high glucose plus transforming growth factor-β-exposed HK-2 cells by reducing apoptotic, fibrotic and inflammatory marker expression. Few DKD-MSC functions were affected by patient characteristics including age, gender, body mass index, hemoglobin A1c, kidney function or urine albumin excretion. However, senescence-associated-β-galactosidase activity was lower in DKD-MSC from participants on metformin therapy. Therefore, while </a><a>DKD altered the transcriptome and migratory function of culture-expanded MSC, DKD-MSC functionality, trophic factor secretion and immunomodulatory activities contributing to repair remained intact. </a>These observations support testing patient-derived MSC therapy and may inform preconditioning regimens in DKD clinical trials.

scholarly journals Diabetic Kidney Disease Alters the Transcriptome and Function of Human Adipose-Derived Mesenchymal Stromal Cells but Maintains Immunomodulatory and Paracrine Activities Important for Renal Repair

2021 ◽  
Author(s):  
LaTonya J. Hickson ◽  
Alfonso Eirin ◽  
Sabena M. Conley ◽  
Timucin Taner ◽  
Xiaohui Bian ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Stromal Cells ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Inflammatory Marker ◽  
Patient Characteristics ◽  
Rna Seq ◽  
Diabetic Kidney

<a>Mesenchymal stem/stromal cells (MSC) facilitate repair in experimental diabetic kidney disease (DKD). However, the hyperglycemic and uremic milieu may diminish regenerative capacity of patient-derived therapy. We hypothesized that DKD reduces human MSC paracrine function. Adipose-derived MSC from 38 DKD participants and 16 controls were assessed for cell surface markers, tri-lineage differentiation, RNA-sequencing (RNA-seq), <i>in vitro</i> function (co-culture or conditioned medium experiments with T cells and human kidney cells [HK-2]), secretome profile, and cellular senescence abundance. The direction of association between MSC function and patient characteristics were also tested. RNA-seq analysis identified 353 differentially expressed genes and downregulation of several immunomodulatory genes/pathways in DKD- <i>vs</i>. Control-MSC. DKD-MSC phenotype, differentiation, and tube formation capacity were preserved but migration was reduced. DKD-MSC with and without interferon-γ priming inhibited T-cell proliferation greater than Control-MSC. DKD-MSC-medium contained higher levels of anti-inflammatory cytokines (indoleamine 2,3-deoxygenase-1 and prostaglandin-E2) and pro-repair factors (hepatocyte growth factor and stromal cell-derived factor-1) but lower Interleukin-6 vs. Control-MSC-medium. DKD-MSC-medium protected high glucose plus transforming growth factor-β-exposed HK-2 cells by reducing apoptotic, fibrotic and inflammatory marker expression. Few DKD-MSC functions were affected by patient characteristics including age, gender, body mass index, hemoglobin A1c, kidney function or urine albumin excretion. However, senescence-associated-β-galactosidase activity was lower in DKD-MSC from participants on metformin therapy. Therefore, while </a><a>DKD altered the transcriptome and migratory function of culture-expanded MSC, DKD-MSC functionality, trophic factor secretion and immunomodulatory activities contributing to repair remained intact. </a>These observations support testing patient-derived MSC therapy and may inform preconditioning regimens in DKD clinical trials.

scholarly journals Aliskiren and perindopril reduce the levels of transforming growth factor-β in patients with non-diabetic kidney disease

2012 ◽  
Vol 25 (6) ◽  
pp. 636-639 ◽  
Author(s):  
Sławomir Lizakowski ◽  
Leszek Tylicki ◽  
Marcin Renke ◽  
Przemysław Rutkowski ◽  
Zbigniew Heleniak ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Diabetic Kidney

scholarly journals MicroRNA in kidney disease

2016 ◽  
Vol 14 (1) ◽  
pp. 8-10 ◽  
Author(s):  
Ingrid Prkacin ◽  
Gordana Cavric ◽  
Nikolina Basic-Jukic
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Kidney Development ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Kidney Fibrosis ◽  
Growth Factor Beta

AbstractClinical and laboratory findings of kidney disease in an adult may find an explanation in kidney functional and/or structural abnormalities that already existed during infancy and childhood, but that may have been missed or underdiagnosed. All the cardiovascular abnormalities that occur in adults with chronic kidney disease are also present in children with chronic kidney disease. Complications in childhood chronic kidney disease will have consequences well beyond pediatric age and influence outcomes of affected young adults with disease. Kidney dysfunction appears early in the course of kidney disease and has been observed in children and adults with chronic kidney disease, condition characterised with kidney fibrosis. Transforming growth factor beta is recognized as a major mediator of kidney fibrosis. New evidence illustrates the relationship between transforming growth factor beta signaling and microRNAs expression during kidney diseases development. MicroRNAs play important roles in kidney development and kidney diseases; they are naturally occurring, 22-nucleotide, noncoding RNAs that mediate posttranscriptional gene regulation. Dysregulation of miRNA expression is an indicator of several diseases including chronic kidney disease. Targeting microRNAs should be a therapeutic potential to ameliorate the disease related to fibrosis. The discovery that circulating miRNAs are detectable in serum and plasma, and that their expression varies as a result of disease, presents great potential to be used as biomarkers in kidney disease prevention and diagnosis.

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