Conclusions
Regenerative performance of most d-USC was significantly lower than normal controls. Understanding the specific changes in d-USC regeneration capability will help elucidate the pathobiology of diabetic nephropathy and lead to prevent USC from diabetic insults, recover the stemness function and also identify novel biomarkers to predict progression of this chronic kidney disease.
Methods
Thirty-six urine samples collected from patients (n=12, age range 60-75 years) with diabetic nephropathy (stages 3-4 stage chronic kidney disease [CKD]) were compared with 30 urine samples from healthy age-matched donors (n=10, age range 60-74 years).
Results
There were approximately six times as many cells in urine samples from patients with diabetic nephropathy, including twice as many USC clones as healthy donors. However, approximately 70% of d-USC had weaker regenerative capacity as assessed by cell proliferation, less secretion of paracrine factors, weaker telomerase activity, and lower renal tubular epithelial differentiation potential compared to healthy controls. In addition, the levels of inflammatory factors (IL-1β and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (p<0.01). Protein levels of autophagy marker (LC3-II) and mTOR signaling molecules (p-mTOR/mTOR, p-Raptor/Raptor and p-S6K1) were significantly lower in patient with diabetic nephropathy (p<0.01). Nevertheless, up to 30% of d-USC possessed similar regenerative capacity as USC from healthy donors. Conclusions: Regenerative performance of most d-USC was significantly lower than normal controls. Understanding the specific changes in d-USC regeneration capability will help elucidate the pathobiology of diabetic nephropathy and lead to prevent USC from diabetic insults, recover the stemness function and also identify novel biomarkers to predict progression of this chronic kidney disease.