Chaperonin-containing t-complex protein-1 subunit β as a possible biomarker for the phase of glomerular hyperfiltration of diabetic nephropathy

Abstract

In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit β (TCP-1β) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1β and type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (C cr), and kidney tissues were harvested for evaluation of TCP-1β expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed that C cr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1β was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

Figure 1

Change of insulin resistance (HOMA-IR) and creatinine clearance (C _cr) in control (C), high-fat diet (HF), and type 2 diabetes mellitus (DM) mice groups. (a) The HOMA-IR levels in HF and DM groups were significantly higher than those in C group on week 1 and week 4 after induction. (b) The change of murine C _Cr in the DM group was significantly higher than in C group on week 4. ^∗ P < 0.05.

Figure 2

Expression of TCP-1β in renal tissue of mice. (a) As the representative Western blot shows, TCP-1β expression in the DM group was higher than in the C group at week 1 and week 4. In addition, TCP-1β expression in the HF group was higher than in C group at week 4. ^∗ P < 0.05. (b) In IHC stain, as the representative pictures show, the expressions of TCP-1β in all groups were predominantly enhanced in the renal tubular region (original magnification, ×400).

Figure 3

Expression of TCP-1β in urine sample in clinical subjects. (a) Urine TCP-1β levels (1-OD) in the group of DM with hyperfiltration were significantly higher as compared with healthy and DM with nonhyperfiltration groups. ^∗∗∗ P < 0.001. (b) The urine TCP-1β (1-OD) level has a significantly positive association with eGFR in subjects with type 2 DM. (r = 0.335, P < 0.001).