Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells
Year: 2023
Type: article
Abstract: BACKGROUND: Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach. METHODS: fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state. RESULTS: RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm). CONCLUSIONS: MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia.
Source: Stem Cell Research & Therapy
Authors: Xiaohui Bian, Sabena M. Conley, Alfonso Eirin, Eric A. Zimmerman Zuckerman, Anastasia L. Smith, Cody C. Gowan, Zachary K. Snow, Tambi Jarmi, Houssam Farres, Young M. Erben, Albert G. Hakaim, Matthew A. Dietz, Abba C. Zubair, Saranya P. Wyles, Joy V. Wolfram, Lilach O. Lerman, LaTonya J. Hickson
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
Awards: G1435962503, G2046173602, G2578633385, G2578853757, Hypoxic preconditioning for the improvement of the regenerative capacity of adipose-derived mesenchymal stem cells and its application in chronic kidney disease due to hypertensive nephropathy, G3026362383, G4514698748, G4670443458, Mesenchymal stem cell senescence in diabetic nephropathy, Obesity-induced mesenchymal stem cell senescence, Coordinating Unit for DiaComp, G7133372848, Renal repair effects of senolytic preconditioned mesenchymal stromal cells in diabetic kidney disease, G8745799326, G9000006656, G9000336804, Mitochondrial injury interferes with endogenous renal repair in experimental renovascular disease
OpenAlex ID: W4353092947