PMID- 17206378 OWN - NLM STAT- MEDLINE DCOM- 20071002 LR - 20220716 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 301 IP - 1-2 DP - 2007 Jul TI - High glucose promotes the production of collagen types I and III by cardiac fibroblasts through a pathway dependent on extracellular-signal-regulated kinase 1/2. PG - 109-14 AB - Hyperglycemia promotes fibrosis by increasing collagen synthesis, a process involving mitogen activated protein kinases (MAPKs). Several studies of diabetic cardiomyopathy have demonstrated an accumulation of collagen, including collagen types I and III, in the myocardium, leading to interstitial fibrosis, which is related to left-ventricular diastolic dysfunction. However, the mechanisms of hyperglycemia-induced collagen production in cardiac fibroblasts are poorly defined. In the present study, neonatal rat cardiac fibroblasts treated with high glucose (25 mM) were assessed by real time PCR and enzyme linked immunosorbent assay (ELISA) showed an increase in both the mRNA and protein level of collagen types I and III. These effects were not due to changes in osmotic pressure. Extracellular signal regulated kinase 1/2 (ERK1/2) was activated by high glucose level (25 mM), and treatment with PD98059 to block ERK phosphorylation significantly inhibited the mRNA and protein expression of collagen types I and III. These results suggest that high glucose accelerates the synthesis of collagen types I and III, and an ERK1/2 cascade in cardiac fibroblasts play an essential role in the control of collagen deposition by high glucose. FAU - Tang, Mengxiong AU - Tang M AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan, China. FAU - Zhang, Wei AU - Zhang W FAU - Lin, Huili AU - Lin H FAU - Jiang, Hong AU - Jiang H FAU - Dai, Hongyan AU - Dai H FAU - Zhang, Yun AU - Zhang Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070106 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Collagen Type I) RN - 0 (Collagen Type III) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (RNA, Messenger) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - IY9XDZ35W2 (Glucose) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Cells, Cultured MH - Collagen Type I/genetics/*metabolism MH - Collagen Type III/genetics/*metabolism MH - Enzyme Inhibitors/metabolism MH - Fibroblasts/cytology/*metabolism MH - Flavonoids/metabolism MH - Glucose/*metabolism MH - Humans MH - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism MH - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism MH - Myocardium/*cytology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Signal Transduction/*physiology EDAT- 2007/01/09 09:00 MHDA- 2007/10/03 09:00 CRDT- 2007/01/09 09:00 PHST- 2006/09/10 00:00 [received] PHST- 2006/12/06 00:00 [accepted] PHST- 2007/01/09 09:00 [pubmed] PHST- 2007/10/03 09:00 [medline] PHST- 2007/01/09 09:00 [entrez] AID - 10.1007/s11010-006-9401-6 [doi] PST - ppublish SO - Mol Cell Biochem. 2007 Jul;301(1-2):109-14. doi: 10.1007/s11010-006-9401-6. Epub 2007 Jan 6.