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

Diabetes ◽  
2021 ◽  
pp. db191268
Author(s):  
LaTonya J. Hickson ◽  
Alfonso Eirin ◽  
Sabena M. Conley ◽  
Timucin Taner ◽  
Xiaohui Bian ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Renal Repair ◽  
And Function

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 Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Riccardo Pofi ◽  
Daniela Fiore ◽  
Rita De Gaetano ◽  
Giuseppe Panio ◽  
Daniele Gianfrilli ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renal Hemodynamics ◽  
Diabetic Kidney ◽  
And Function ◽  
Phosphodiesterase 5

scholarly journals Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Man Wu ◽  
Minjie Zhang ◽  
Yaozhi Zhang ◽  
Zixian Li ◽  
Xingyu Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Cell Metabolism ◽  
Renal Diseases ◽  
Future Research ◽  
Lysosomal Function ◽  
Diabetic Kidney ◽  
Effective Interventions ◽  
Proximal Tubular Epithelial Cells ◽  
And Function

AbstractLysosomes are organelles involved in cell metabolism, waste degradation, and cellular material circulation. They play a key role in the maintenance of cellular physiological homeostasis. Compared with the lysosomal content of other organs, that of the kidney is abundant, and lysosomal abnormalities are associated with the occurrence and development of certain renal diseases. Lysosomal structure and function in intrinsic renal cells are impaired in diabetic kidney disease (DKD). Promoting lysosomal biosynthesis and/or restoring lysosomal function can repair damaged podocytes and proximal tubular epithelial cells, and delay the progression of DKD. Lysosomal homeostasis maintenance may be advantageous in alleviating DKD. Here, we systematically reviewed the latest advances in the relationship between lysosomal dyshomeostasis and progression of DKD based on recent literature to further elucidate the mechanism of renal injury in diabetes mellitus and to highlight the application potential of lysosomal homeostasis maintenance as a new prevention and treatment strategy for DKD. However, research on screening effective interventions for lysosomal dyshomeostasis is still in its infancy, and thus should be the focus of future research studies. The screening out of cell-specific lysosomal function regulation targets according to the different stages of DKD, so as to realize the controllable targeted regulation of cell lysosomal function during DKD, is the key to the successful clinical development of this therapeutic strategy.

Systems Medicine Derived Biomarkers to Assess How Canagliflozin Delays Progression of Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1126-P
Author(s):  
HIDDO LAMBERS. HEERSPINK ◽  
PAUL PERCO ◽  
JOHANNES LEIERER ◽  
MICHAEL K. HANSEN ◽  
ANDREAS HEINZEL ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Systems Medicine ◽  
Diabetic Kidney

Factors Related to the High Prevalence of Diabetic Kidney Disease in Ecuador-Update for Health Policy Makers

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 526-P
Author(s):  
MARIANA E. GUADALUPE ◽  
GRACIELA B. ALVAREZ CONDO ◽  
FANNY E. VERA LORENTI ◽  
BETTY J. PAZMIÑO GOMEZ ◽  
EDGAR I. RODAS NEIRA ◽  
...  
Keyword(s):  
Health Policy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Policy Makers ◽  
Diabetic Kidney ◽  
High Prevalence

Albuminuria Is More Closely Associated with Vascular Endothelial Function than eGFR in Type 2 Diabetes with Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Diabetic Kidney Disease ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Diabetic Kidney

539-P: The Trend of Diabetic Kidney Disease with Low eGFR and Absence of Albuminuria in Type 2 Diabetic Patients in Japan from 1996-2015

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Diabetic Kidney ◽  
Type 2 Diabetic

236-OR: Effects of Dapagliflozin on Progression of Diabetic Kidney Disease: Analysis from DECLARE-TIMI 58 Trial

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 236-OR
Author(s):  
OFRI MOSENZON ◽  
STEPHEN D. WIVIOTT ◽  
THOMAS A. ZELNIKER ◽  
HIDDO L. HEERSPINK ◽  
JAMIE P. DWYER ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Disease Analysis
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