Chinese Medical Sciences Journal ›› 2020, Vol. 35 ›› Issue (1): 31-42.doi: 10.24920/003573
• Original Article • Previous Articles Next Articles
Hao Qiufa, Wang Baobao, Zhang Wei, Qiu Wei, Liu Qianling, Li Xuemei()
Received:
2019-04-02
Published:
2020-03-31
Online:
2020-02-29
Contact:
Li Xuemei
E-mail:professorliunion@163.com
In this study, the authors aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules in type 2 diabetic nephropathy. They observed the upregulation of inflammatory factor NF-κB p65, the decreased phosphorylation of AKT (s473), and the reduction of albumin receptors AMN-cubilin in db/db mouse kidneys and tumor necrosis factor α stimulating HKC cells. Furthermore, they found nuclear factor kappa-B inhibitor parthenolide could mitigate inflammation and remodel impaired insulin signaling, and promote the expression of cubilin in db/db mice and improve the albumin uptake in renal tubule cells. These results indicate that inflammation impairing insulin signaling may be one of the mechanisms that accounts for the reduction in tubular albumin reabsorption in the early stage of diabetic nephropathy. |
Hao Qiufa, Wang Baobao, Zhang Wei, Qiu Wei, Liu Qianling, Li Xuemei. NF-κB Inhibitor Parthenolide Promotes Renal Tubules Albumin Uptake in Type 2 Diabetic Nephropathy[J].Chinese Medical Sciences Journal, 2020, 35(1): 31-42.
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Table 1
Comparisons of metabolic and renal parameters among the three 16-week-old mice groups§"
Groups | n | Blood glucose (mmol/L) | Serum insulin (mIU/L) | HOMA-IR | Serum creatinine (μmol/L) | UACR (mg/mmol) |
---|---|---|---|---|---|---|
db/m | 5 | 10.01±1.73 | 14.93±4.00 | 6.60±1.70 | 9.56±0.98 | 19.5±14.5 |
db/db | 8 | 41.19±7.31* | 21.02±9.95 | 36.83±14.09* | 7.20±2.82 | 190.3±7.3* |
db/db+PTN | 8 | 41.00±14.78 | 21.30±7.30 | 31.07±28.05 | 7.56±2.42 | 143.0±97.6 |
F value | 17.323 | 0.277 | 3.881 | 1.655 | 2.419 | |
P value | <0.001 | 0.761 | 0.042 | 0.222 | 0.121 |
Figure 1.
Histopathological changes of the kidney in mice. Under periodic acid-Schiff staining, the db/db mice kidney demonstrated the glomerular hypertrophy and the increase of mesangial matrix. PTN could alleviate the above pathological changes in kidneys of the db/db mice. (PAS staining, 200×)"
Figure 2.
Expressions of NF-κB p65, p-AKT/AKT, AMN and cubilin in mice kidney were detected by immunohistochemstry (A, 200×) and western blots (B). n=3 for each group. Results of immunofluorescence for albumin uptake in renal tubules (C). White arrows indicate uptake of albumin in renal tubules. NF-κB: nuclear factor kappa-B; AMN: amnionless. *P<0.05 compared with the db/m group; #P<0.05 compared with the db/db group."
Figure 3.
Albumin (Alb) endocytosis and expression of AMN-cubilin in HKC cells with insulin treatment. Results of fluorometric measurement (A) and western blots (B) for detecting albumin uptake in HKC cells. Western bloting results of p-AKT/AKT, AMN and cubilin expressions in HKC cells (C). n=3 for each group. *P<0.05 compared with the group without insulin treatment."
Figure 4.
Albumin endocytosis in HKC cells with treatment of TNF-α and PTN. Viability of HKC cells treated with tumor necrosis factor (TNF-α, A) or parthenolide (PTN, B). Fluorometric measurement (C, D) and western blots (E) of albumin uptake in HKC cells of the insulin, TNF-α and PTN+TNF-α groups. HKC cells in the PTN+TNF-α group were treated with TNF-α and PTN simultaneously for 18 hours, and then treated with insulin for 30 minutes. n=3 for each group. *P<0.05 compared with the insulin group; #P<0.05 compared with the TNF-α group."
Figure 5.
Expression of AMN-cubilin, NF-κB p65, and phosphorylation of AKT and IRS-1 in HKC cells with treatment of TNF-α and PTN detected by Western blot. HKC cells were treated with TNF-α and PTN simultaneously for 18 hours, and then treated with insulin for 30 minutes. n=3 for each group. *P<0.05 compared with the insulin group; #P<0.05 compared with the TNF-α group."
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