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Expression of farnesyl pyrophosphate synthase is increased in diabetic cardiomyopathy
Author(s) -
Li Zhengwei,
Zhang Jiefang,
Wang Min,
Qiu Fuyu,
Jin Chongyin,
Fu Guosheng
Publication year - 2021
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11573
Subject(s) - farnesyl pyrophosphate , diabetic cardiomyopathy , gene knockdown , signal transduction , glycogen synthase , chemistry , mevalonate pathway , cardiomyopathy , in vivo , microbiology and biotechnology , biochemistry , pharmacology , cancer research , atp synthase , phosphorylation , medicine , biology , enzyme , heart failure , biosynthesis , apoptosis
Farnesyl pyrophosphate synthase (FPPS)‐catalyzed isoprenoid intermediates are involved in diabetic cardiomyopathy. This study investigated the specific role of FPPS in the development of diabetic cardiomyopathy. We demonstrated that FPPS expression was elevated in both in vivo and in vitro models of diabetic cardiomyopathy. FPPS inhibition decreased the expression of proteins related to cardiac fibrosis and cardiomyocytic hypertrophy, including collagen I, collagen III, connective tissue growth factor, natriuretic factor, brain natriuretic peptide, and β‐myosin heavy chain. Furthermore, FPPS inhibition and knockdown prevented phosphorylated c‐Jun N‐terminal kinase 1/2 (JNK1/2) activation in vitro. In addition, a JNK1/2 inhibitor downregulated high‐glucose‐induced responses to diabetic cardiomyopathy. Finally, immunofluorescence revealed that cardiomyocytic size was elevated by high glucose and was decreased by zoledronate, small‐interfering farnesyl pyrophosphate synthase (siFPPS), and a JNK1/2 inhibitor. Taken together, our findings indicate that FPPS and JNK1/2 may be part of a signaling pathway that plays an important role in diabetic cardiomyopathy.