Synergistic Effects of Combining Anti-Midkine and Hepatocyte Growth Factor Therapies Against Diabetic Nephropathy in Rats.

作者: Xiaojun Ren , Hui Li , Ping Feng , Junwei Wang , Zhaowei Meng

DOI: 10.1097/MAJ.0000000000000510

关键词:

摘要: Abstract: Purpose This study aimed to assess whether synergism could be achieved when combining midkine (MK) antisense oligodeoxynucleotides (anti-MK ODN) and recombinant human hepatocyte growth factor (HGF) in diabetic nephropathy (DN) rat models. Methods Rats were randomized into 6 groups: control, DN rats without treatment, treated with scrambled ODN, anti-MK HGF ODN plus HGF. models created by intraperitoneal injection of streptozotocin. Two weeks later, treatments commenced. (1 mg/kg) was intravenously injected weekly for 4 weeks. (500 μg/kg) subcutaneously daily Eight euthanized. Serum urine parameters, kidney histopathological injury scores, immunohistochemistry protein expressions measured. Results Blood glucose, creatinine, blood urea nitrogen albumin significantly elevated rats. Any single treatment markedly reduced their levels, yet combined decreased them further. monotherapy decrease renal score positive percentage, although the most prominent change displayed combinational therapy. Western blot showed expression MK Anti-MK suppressed significantly. The serum concentrations transforming factor-β1 connective tissue between therapy significant. Conclusions demonstrated that gene suppressing synergistically attenuates may provide a novel avenue designing future therapeutic regimens against DN.

参考文章(63)
Bi-cheng LIU, Hai-quan HUANG, Dong-dong LUO, Kun-ling MA, Dian-ge LIU, Hong LIU, Connective tissue growth factor is associated with the early renal hypertrophy in uninephrectomized diabetic rats. Chinese Medical Journal. ,vol. 119, pp. 1010- 1016 ,(2006) , 10.1097/00029330-200606020-00008
Takashi Muramatsu, Kenji Kadomatsu, Midkine: an emerging target of drug development for treatment of multiple diseases. British Journal of Pharmacology. ,vol. 171, pp. 811- 813 ,(2014) , 10.1111/BPH.12571
T Muramatsu, Structure and function of midkine as the basis of its pharmacological effects British Journal of Pharmacology. ,vol. 171, pp. 814- 826 ,(2014) , 10.1111/BPH.12353
Waichi Sato, Kenji Kadomatsu, Yukio Yuzawa, Hisako Muramatsu, Nigishi Hotta, Seiichi Matsuo, Takashi Muramatsu, Midkine Is Involved in Neutrophil Infiltration into the Tubulointerstitium in Ischemic Renal Injury The Journal of Immunology. ,vol. 167, pp. 3463- 3469 ,(2001) , 10.4049/JIMMUNOL.167.6.3463
Giuseppe Remuzzi, Arrigo Schieppati, Piero Ruggenenti, Nephropathy in Patients with Type 2 Diabetes New England Journal of Medicine. ,vol. 346, pp. 1145- 1151 ,(2002) , 10.1056/NEJMCP011773
Youhua Liu, Krupa Rajur, Evelyn Tolbert, Lance D. Dworkin, Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney International. ,vol. 58, pp. 2028- 2043 ,(2000) , 10.1111/J.1523-1755.2000.00375.X
P. Roestenberg, F. A. van Nieuwenhoven, L. Wieten, P. Boer, T. Diekman, A. M. Tiller, W. M. Wiersinga, N. Oliver, W. Usinger, S. Weitz, R. O. Schlingemann, R. Goldschmeding, Connective Tissue Growth Factor Is Increased in Plasma of Type 1 Diabetic Patients With Nephropathy Diabetes Care. ,vol. 27, pp. 1164- 1170 ,(2004) , 10.2337/DIACARE.27.5.1164
Akinori Hobo, Yukio Yuzawa, Tomoki Kosugi, Noritoshi Kato, Naoto Asai, Waichi Sato, Shoichi Maruyama, Yasuhiko Ito, Hiroyuki Kobori, Shinya Ikematsu, Akira Nishiyama, Seiichi Matsuo, Kenji Kadomatsu, The growth factor midkine regulates the renin-angiotensin system in mice Journal of Clinical Investigation. ,vol. 119, pp. 1616- 1625 ,(2009) , 10.1172/JCI37249
Sami T. Azar, Ibrahim Salti, Mira S. Zantout, Stella Major, Alterations in Plasma Transforming Growth Factor β in Normoalbuminuric Type 1 and Type 2 Diabetic Patients The Journal of Clinical Endocrinology and Metabolism. ,vol. 85, pp. 4680- 4682 ,(2000) , 10.1210/JCEM.85.12.7073