Evidence for the involvement of JAK/STAT/SOCS pathway in the mechanism of Tangshen formula-treated diabetic nephropathy.
Diabetic nephropathy is one of the most significant microvascular complications associated with diabetes. Until now, there is no effective treatment and the gene mechanism of diabetic nephropathy is still unclear. Tangshen formula is a traditional Chinese medicine, and has been shown to have good clinical efficacy in diabetic nephropathy treatment. The objective of this study was to investigate the changes of gene expression profiling and explore the molecular mechanism using a db/db mice model treated by Tangshen formula. After administration for 12 weeks, a microarray was applied to detect the gene expression of db/db mice kidney tissues. Quantitative real-time PCR was used to confirm the differential gene expression and carry out a JAK/STAT/SOCS signaling pathway study. Treatment with Tangshen formula reduced the levels of serum glucose and urinary albumin in db/db mice, and the effects of Tangshen formula on db/db mice were significantly different from the positive control (Losartan potassium tablets) on microarray data. It also showed that the JAK/STAT/SOCS signaling pathway played an important role in the treatment process. The expressions of JAK1, JAK2, and STAT3 were upregulated, and STAT4 was downregulated in Tangshen formula-treated db/db mice. SOCS1, 3, and 7 were all activated, while negative feedback regulated other related genes in the JAK/STAT/SOCS pathway. Our study suggested that Tangshen formula has beneficial effects on diabetic nephropathy treatment via regulating the JAK/STAT/SOCS signaling pathway. This study will help to provide evidence-based recommendations for Tangshen formula clinical treatment.
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China.
Jingjing
J
Hu
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, P. R. China.
Xuemei
X
Fan
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China.
Xiansheng
X
Meng
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, P. R. China.
Yiming
Y
Wang
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, P. R. China.
Qionglin
Q
Liang
State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, P. R. China.
Guoan
G
Luo
D000818:Animals; D016000:Cluster Analysis; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053612:Janus Kinases / Q000235:genetics; D007668:Kidney / Q000187:drug effects; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010946:Plants, Medicinal / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
D004365:Drugs, Chinese Herbal; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases