Diabetes, Vol 48, Issue 3 595-602, Copyright © 1999 by American Diabetes Association

ARTICLES

Stretch-induced overproduction of fibronectin in mesangial cells is mediated by the activation of mitogen-activated protein kinase

T Ishida, M Haneda, S Maeda, D Koya and R Kikkawa
Third Department of Medicine, Shiga University of Medical Science, Otsu, Japan.

An excessive production of extracellular matrix (ECM) proteins in glomerular mesangial cells is considered to be responsible for the development of mesangial expansion seen in diabetic nephropathy. Mechanical stretch due to glomerular hypertension has been proposed as one of the factors leading to an increase in the production of ECM proteins in mesangial cells, but the precise mechanism of stretch-induced overproduction of ECM proteins has not been elucidated. Herein, we provide the evidence that mitogen-activated protein kinase (MAPK) may play a key role in the overproduction of fibronectin (FN) in mesangial cells exposed to mechanical stretch. MAPK, also termed extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), was activated by mechanical stretch in time- and intensity-dependent manners. Stretch-induced activation of ERK was inhibited by herbimycin A, a tyrosine kinase inhibitor, but not by GF109203X or calphostin C, the inhibitors of protein kinase C. Mechanical stretch also enhanced DNA-binding activity of AP-1, and this enhancement was inhibited by PD98059, an inhibitor of MAPK or ERK kinase (MEK). Furthermore, mechanical stretch stimulated the expression of FN mRNA followed by a significant increase in its protein accumulation. PD98059 could prevent stretch-induced increase in the expression of FN mRNA and protein. These results indicate that the activation of ERK may mediate the overproduction of ECM proteins in mesangial cells exposed to mechanical stretch, an in vitro model for glomerular hypertension seen in diabetes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. C. Krepinsky, Y. Li, Y. Chang, L. Liu, F. Peng, D. Wu, D. Tang, J. Scholey, and A. J. Ingram Akt Mediates Mechanical Strain-Induced Collagen Production by Mesangial Cells J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1661 - 1672. [Abstract] [Full Text] [PDF]

				M. Negishi, H. Shimizu, S. Okada, A. Kuwabara, F. Okajima, and M. Mori 9HODE Stimulates Cell Proliferation and Extracellular Matrix Synthesis in Human Mesangial Cells via PPAR{gamma} Experimental Biology and Medicine, November 1, 2004; 229(10): 1053 - 1060. [Abstract] [Full Text] [PDF]

				H. Fujita, S. Omori, K. Ishikura, M. Hida, and M. Awazu ERK and p38 mediate high-glucose-induced hypertrophy and TGF-{beta} expression in renal tubular cells Am J Physiol Renal Physiol, January 1, 2004; 286(1): F120 - F126. [Abstract] [Full Text] [PDF]

				K. Takaya, D. Koya, M. Isono, T. Sugimoto, T. Sugaya, A. Kashiwagi, and M. Haneda Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells Am J Physiol Renal Physiol, May 1, 2003; 284(5): F1037 - F1045. [Abstract] [Full Text] [PDF]

				A. D. Oldenhof, O. P. Shynlova, M. Liu, B. L. Langille, and S. J. Lye Mitogen-activated protein kinases mediate stretch-induced c-fos mRNA expression in myometrial smooth muscle cells Am J Physiol Cell Physiol, November 1, 2002; 283(5): C1530 - C1539. [Abstract] [Full Text] [PDF]

				U. Uhlig, J.J. Haitsma, T. Goldmann, D.L. Poelma, B. Lachmann, and S. Uhlig Ventilation-induced activation of the mitogen-activated protein kinase pathway Eur. Respir. J., October 1, 2002; 20(4): 946 - 956. [Abstract] [Full Text] [PDF]

				M. Zayzafoon, S. Botolin, and L. R. McCabe p38 and Activating Transcription Factor-2 Involvement in Osteoblast Osmotic Response to Elevated Extracellular Glucose J. Biol. Chem., September 27, 2002; 277(40): 37212 - 37218. [Abstract] [Full Text] [PDF]

				J. Krepinsky, A. J. Ingram, L. James, H. Ly, K. Thai, D. C. Cattran, J. A. Miller, and J. W. Scholey 17beta -Estradiol Modulates Mechanical Strain-induced MAPK Activation in Mesangial Cells J. Biol. Chem., March 8, 2002; 277(11): 9387 - 9394. [Abstract] [Full Text] [PDF]

				T. Tawadros, A. Formenton, J. Dudler, N. Thompson, P. Nicod, H.-J. Leisinger, G. Waeber, and J.-A. Haefliger The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed urothelium J. Cell Sci., January 15, 2002; 115(2): 385 - 393. [Abstract] [Full Text] [PDF]

				N. Kushida, Y. Kabuyama, O. Yamaguchi, and Y. Homma Essential role for extracellular Ca2+ in JNK activation by mechanical stretch in bladder smooth muscle cells Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1165 - C1172. [Abstract] [Full Text] [PDF]

				M. D. Boppart, M. F. Hirshman, K. Sakamoto, R. A. Fielding, and L. J. Goodyear Static stretch increases c-Jun NH2-terminal kinase activity and p38 phosphorylation in rat skeletal muscle Am J Physiol Cell Physiol, February 1, 2001; 280(2): C352 - C358. [Abstract] [Full Text] [PDF]

				B. L. Riser, J. Varani, P. Cortes, J. Yee, M. Dame, and A. K. Sharba Cyclic Stretching of Mesangial Cells Up-Regulates Intercellular Adhesion Molecule-1 and Leukocyte Adherence : A Possible New Mechanism for Glomerulosclerosis Am. J. Pathol., January 1, 2001; 158(1): 11 - 17. [Abstract] [Full Text] [PDF]

				M. ISONO, M. C. I.-D. L. CRUZ, S. CHEN, S. W. HONG, and F. N. ZIYADEH Extracellular Signal-Regulated Kinase Mediates Stimulation of TGF-{beta}1 and Matrix by High Glucose in Mesangial Cells J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2222 - 2230. [Abstract] [Full Text]

				W. Tian, Z. Zhang, and D. M. Cohen MAPK signaling and the kidney Am J Physiol Renal Physiol, October 1, 2000; 279(4): F593 - F604. [Abstract] [Full Text] [PDF]

				J. A. Dlugosz, S. Munk, J. Kapor-Drezgic, H. J. Goldberg, I. G. Fantus, J. W. Scholey, and C. I. Whiteside Stretch-induced mesangial cell ERK1/ERK2 activation is enhanced in high glucose by decreased dephosphorylation Am J Physiol Renal Physiol, October 1, 2000; 279(4): F688 - F697. [Abstract] [Full Text] [PDF]