Activation of S6 kinase by repeated cycles of stretching and relaxation in rat glomerular mesangial cells. Evidence for involvement of protein kinase C

Homma, Teiichi; Akai, Youichi; Burns, Kevin D.; Harris, Raymond C.

doi:10.1016/s0021-9258(18)50066-1

Cited by 50 publications

(2 citation statements)

References 47 publications

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“…Intraglomerular pressure is transmitted to the capillary walls by Laplace's law and results in mechanical stretch to glomerular mesangial cells [30,31]. It has been shown that mesangial cells in culture, when they are exposed to mechanical stretch, exhibit alterations in cell morphology, proliferation and activation of S6 kinase and expression of protooncogenes or cyclooxygenase [31][32][33]. Moreover, it is demonstrated that mesangial cells undergoing cyclic stretching increase the synthesis of types I and IV collagen, laminin and fibronectin, major components of ECM [31].…”

Section: Fig 2 Effect Of Stretch On Mrna Expression Of Extracellular Matrix (Ecm) Components and Transforming Growth Factor-␤1 (Tgf-␤1)mentioning

confidence: 99%

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Hori¹,

Katoh²,

Hirakata³

et al. 1998

Kidney International

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Transforming growth factor-beta (TGF-beta) is usually secreted as a large latent complex associated with latent TGF-beta binding protein-1 (LTBP-1), which is known to bind to extracellular matrix (ECM) components. Although the LTBP-ECM interaction has been suggested to play a role in the activation and biological action of TGF-beta, the precise mechanism is still unclear. In glomerular hypertension mesangial cells are believed to perceive the increased cyclic strain and we have recently reported that cyclic mechanical stretch in vitro enhances the expression of ECM components via an autocrine/paracrine secretion of TGF-beta in cultured rat mesangial cells. Therefore, in this study we examined the role of LTBP-1 in the stretch-induced, TGF-beta-mediated ECM expression. Mesangial cells expressed mRNA for short and long forms of LTBP-1 (LTBP-1S and LTBP-1L, respectively). Mesangial cells were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles/min for 24 to 36 hours in the presence of polyclonal antibody raised against human LTBP-1 or synthetic oligopeptides corresponding to the N-terminal portions of human LTBP-1, which may work as competitive inhibitors against the LTBP-ECM association. Both anti-LTBP-1 antibody (Ab39) and synthetic oligopeptides inhibited the stretch-induced mRNA expression of type I collagen and fibronectin in a dose-dependent manner, but the inhibition by Ab39 or the oligopeptides was recovered by adding recombinant TGF-beta. Ab39 or the oligopeptides did not change the effect of exogenously added TGF-beta, such as growth-inhibition in mink lung epithelial cells. These results suggest that mesangial cells secrete TGF-beta as a large latent complex, and the LTBP-ECM interaction may be a pivotal step in TGF-beta action and ECM accumulation, providing a new therapeutic strategy against progression of glomerulosclerosis and other fibrotic diseases.

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Section: Fig 2 Effect Of Stretch On Mrna Expression Of Extracellular Matrix (Ecm) Components and Transforming Growth Factor-␤1 (Tgf-␤1)mentioning

confidence: 99%

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Hori¹,

Katoh²,

Hirakata³

et al. 1998

Kidney International

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“…Abbreviation~ used in th/s paper: cAMP, cyclic AMP; cPLA2, cytoplasmic phospholipase A2; IBMX, 3-isobutylA-methoxanthine; LDH, lactic dehydrogenase; PGE2, prostaglandin E2; PICA, protein kinase A. (Homma et al, 1992;Rosales and Sumpio, 1992;Kroll et al, 1993). Some studies also indicate increased production of cyclic AMP (cAMP) (Watson, 1990;Ngan et al, 1990).…”

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confidence: 99%

Stress relaxation of fibroblasts activates a cyclic AMP signaling pathway.

Grinnell

1994

The Journal of Cell Biology

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Abstract. Mechanical force regulates gene expression and cell proliferation in a variety of cell types, but the mechanotransducers and signaling mechanisms involved are highly speculative. We studied the fibroblast signaling mechanism that is activated when cells are switched from mechanically stressed to mechanically relaxed conditions, i.e., stress relaxation. Within I0 min after initiation of stress relaxation, we observed a transient 10-20-fold increase in cytoplasmic cyclic AMP (cAMP) and a threefold increase in protein kinase A activity. The increase in cAMP depended on stimulation of adenylyl cyclase rather than inhibition of phosphodiesterase. Generation of cAMP was inhibited by indomethacin, and release of arachidonic acid was found to be an upstream step of the pathway. Activation of signaling also depended on influx of extracellular Ca 2+ because addition of EGTA to the incubations at concentrations just sufficient to exceed Ca 2+ in the medium inhibited the stress relaxation-dependent increase in free arachidonic acid and cAMP. This inhibition was overcome by adding CaC12 to the medium. On the other hand, treating fibroblasts in mechanically stressed cultures with the calcium ionophore A23187-stimulated arachidonic acid and cAMP production even without stress relaxation. In summary, our results show that fibroblast stress relaxation results in activation of a Ca2+-dependent, adenylyl cyclase signaling pathway. Overall, the effect of stress relaxation on cAMP and PKA levels was equivalent to that observed after treatment of cells with forskolin.

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Pulsatile Stretch Activates Mitogen-Activated Protein Kinase (MAPK) Family Members and Focal Adhesion Kinase (p125FAK) in Cultured Rat Cardiac Myocytes

Seko

Takahashi

et al. 1999

Biochemical and Biophysical Research Communications

142

102

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Activation of S6 kinase by repeated cycles of stretching and relaxation in rat glomerular mesangial cells. Evidence for involvement of protein kinase C

Cited by 50 publications

References 47 publications

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Stress relaxation of fibroblasts activates a cyclic AMP signaling pathway.

Pulsatile Stretch Activates Mitogen-Activated Protein Kinase (MAPK) Family Members and Focal Adhesion Kinase (p125FAK) in Cultured Rat Cardiac Myocytes

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