Study on PINK1 Expression and Its Clinical Value in Diabetic Nephropathy

Authors

  • Dongmei Xu Department of Endocrinology, Longquan City People’s Hospital, Longquan, Zhejiang, 323799, China. Author
  • Feng Cai Department of Endocrinology, Longquan City People’s Hospital, Longquan, Zhejiang, 323799, China. Author
  • Jiexi Hu Department of Endocrinology, Longquan City People’s Hospital, Longquan, Zhejiang, 323799, China. Author
  • Zhihong Zeng Department of Endocrinology, Longquan City People’s Hospital, Longquan, Zhejiang, 323799, China. Author

DOI:

https://doi.org/10.5254/0x69c976

Keywords:

Diabetic nephropathy, Inflammatory factors, Mitochondrial membrane potential, PINK1, ROS

Abstract

Introduction. To explore PTEN-induced putative kinase 1 (PINK1) expression and its clinical value in diabetic nephropathy.

Methods. Ninety patients with diabetic nephropathy were recruited and divided into metformin hydrochloride monotherapy group, telmisartan monotherapy group and combination therapy (metformin and telmisartan) group. Renal function indices and PINK1 expression, inflammatory factors, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels were detected. The correlation between PINK1 and inflammatory factors, renal function indicators including estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and serum creatinine (SCr)] were analyzed by Pearson correlation.

Results. Following treatments, the combination therapy group exhibited increased PINK1 expression levels and decreased ROS levels compared to the groups receiving metformin hydrochloride or telmisartan monotherapy. The combination therapy group showed significant improvements in renal function indices and inflammatory markers. Additionally, the MMP ratio in the combination therapy group was higher compared to the two monotherapy groups. Furthermore, PINK1 was negatively correlated with UACR, SCr, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), while positively correlated with eGFR and interleukin-2 (IL-2).

Conclusion. PINK1 exhibits low expression levels in patients with diabetic nephropathy and its expression is strongly associated with the inhibition of disease progression, thereby offering significant clinical diagnostic value. Additionally, it may serve as a potential biological marker for clinical diagnosis and treatment of diabetic nephropathy.

Downloads

References

1. Li, X., et al., Epigenetics in the pathogenesis of diabetic nephropathy. Acta Biochim Biophys Sin (Shanghai), 2022. 54(2): p. 163-172.

2. Qi, C., et al., Classification and Differential Diagnosis of Diabetic Nephropathy. J Diabetes Res, 2017. 2017: p. 8637138.

3. Khan, N.U., et al., Insights into predicting diabetic nephropathy using urinary biomarkers. Biochim Biophys Acta Proteins Proteom, 2020. 1868(10): p. 140475.

4. Samsu, N., Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Res Int, 2021. 2021: p. 1497449.

5. Audzeyenka, I., A. Bierżyńska, and A.C. Lay, Podocyte Bioenergetics in the Development of Diabetic Nephropathy: The Role of Mitochondria. Endocrinology, 2022. 163(1).

6. Li, C., et al., PACS-2 Ameliorates Tubular Injury by Facilitating Endoplasmic Reticulum-Mitochondria Contact and Mitophagy in Diabetic Nephropathy. Diabetes, 2022. 71(5): p. 1034-1050.

7. Ahmad, A.A., S.O. Draves, and M. Rosca, Mitochondria in Diabetic Kidney Disease. Cells, 2021. 10(11).

8. Kim, K. and E.Y. Lee, Excessively Enlarged Mitochondria in the Kidneys of Diabetic Nephropathy. Antioxidants

(Basel), 2021. 10(5).

9. Yang, B., Y. Chen, and J. Shi, Reactive Oxygen Species (ROS)-Based Nanomedicine. Chem Rev, 2019. 119(8): p. 4881-4985.

tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biol, 2018. 16: p. 32-46.

10. Han, Y., et al., Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biol, 2018. 16: p. 32-46.

11. Gan, Z.Y., et al., Activation mechanism of PINK1. Nature, 2022. 602(7896): p. 328-335.

12. Harbauer, A.B., et al., Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy. Neuron, 2022. 110(9): p. 1516-1531.e9.

13. Barazzuol, L., et al., PINK1/Parkin Mediated Mitophagy, Ca(2+) Signalling, and ER-Mitochondria Contacts in Parkinson’s Disease. Int J Mol Sci, 2020. 21(5).

14. Xiao, L., et al., The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biol, 2017. 11: p. 297-311.

15. Reddy, V.K.K., et al., Investigating Interleukin-6 Levels

in Type 2 Diabetes Mellitus Patients With and Without Diabetic Nephropathy. Cureus, 2024. 16(8): p. e67014.

16. Jin, Q., et al., Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols. Front Immunol, 2023. 14: p. 1185317.

17. Gross, J.L., et al., Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care, 2005. 28(1): p. 164-76.

18. Balakumar, P., H.K. Bishnoi, and N. Mahadevan, Telmisartan in the management of diabetic nephropathy: a contemporary view. Curr Diabetes Rev, 2012. 8(3): p. 183- 90.

19. Zha, D., et al., Telmisartan attenuates diabetic nephropathy progression by inhibiting the dimerization of angiotensin type-1 receptor and adiponectin receptor-1. Life Sci, 2019. 221: p. 109-120.

20. Kawanami, D., Y. Takashi, and M. Tanabe, Significance of Metformin Use in Diabetic Kidney Disease. Int J Mol Sci, 2020. 21(12).

21. Mohammad, H.M.F., et al., Metformin suppresses LRG1 and TGFβ1/ALK1-induced angiogenesis and protects against ultrastructural changes in rat diabetic nephropathy. Biomed Pharmacother, 2023. 158: p. 114128.

22. Jianfang, F., et al., Effect and Safety of Pioglitazone-Metformin Tablets in the Treatment of Newly Diagnosed Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease in Shaanxi Province: A Randomized, Double-Blinded, Double-Simulated Multicenter Study. J Diabetes Res, 2023. 2023: p. 2044090.

23. Sahay, R.K., et al., Fixed-Dose Combination of Dapagliflozin + Sitagliptin + Metformin in Patients with Type 2 Diabetes Poorly Controlled with Metformin: Phase 3, Randomized Comparison with Dual Combinations. Adv Ther, 2023. 40(7): p. 3227-3246.

24. Yang, S., et al., Mitochondria: A Novel Therapeutic Target n Diabetic Nephropathy. Curr Med Chem, 2017. 24(29): p. 3185-3202.25.

25. Zhou, Y., et al., Metrnl Alleviates Lipid Accumulation by Modulating Mitochondrial Homeostasis in Diabetic Nephropathy. Diabetes, 2023. 72(5): p. 611-626.

26. Tang, H., et al., Melatonin alleviates renal injury by activating mitophagy in diabetic nephropathy. Front Endocrinol (Lausanne), 2022. 13: p. 889729.

27. Zhu, Z., et al., Huangkui capsule attenuates diabetic kidney disease through the induction of mitophagy mediated by STING1/PINK1 signaling in tubular cells. Phytomedicine, 2023. 119: p. 154975.

28. Zhong, Y., et al., Dioscin relieves diabetic nephropathy via suppressing oxidative stress and apoptosis, and improving mitochondrial quality and quantity control. Food Funct, 2022. 13(6): p. 3660-3673.

29. Wada, J. and H. Makino, Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond), 2013. 124(3): p. 139-52.

30. Rayego-Mateos, S., et al., Targeting inflammation to treat diabetic kidney disease: the road to 2030. Kidney Int, 2023. 103(2): p. 282-296.

31. Antar, S.A., et al., Telmisartan attenuates diabetic nephropathy by mitigating oxidative stress and inflammation, and upregulating Nrf2/HO-1 signaling in diabetic rats. Life Sci, 2022. 291: p. 120260.

32. Zhan, X., et al., Telmisartan Mitigates High-Glucose-Induced Injury in Renal Glomerular Endothelial Cells

(rGECs) and Albuminuria in Diabetes Mice. Chem Res Toxicol, 2021. 34(9): p. 2079-2086.

33. Alhaider, A.A., et al., Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact, 2011. 192(3): p. 233-42.

34. Sung, M.J., et al., PTEN-induced kinase 1 exerts protective effects in diabetic kidney disease by attenuating mitochondrial dysfunction and necroptosis. Int J Biol Sci, 2023. 19(16): p. 5145-5159.

35. Audzeyenka, I., et al., PTEN-induced kinase 1 deficiency alters albumin permeability and insulin signaling in podocytes. J Mol Med (Berl), 2022. 100(6): p. 903-915.

Downloads

Published

2024-10-18

Issue

Section

ORIGINAL | Kidney Diseases

How to Cite

Study on PINK1 Expression and Its Clinical Value in Diabetic Nephropathy. (2024). Iranian Journal of Kidney Diseases, 18(05). https://doi.org/10.5254/0x69c976

Similar Articles

1-10 of 520

You may also start an advanced similarity search for this article.