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991.
Bruce L. Riser Feridoon Najmabadi Bernard Perbal Jo Ann Rambow Melisa L. Riser Ernest Sukowski Herman Yeger Sarah C. Riser Darryl R. Peterson 《Journal of cell communication and signaling》2010,4(1):39-50
Prior work in the CCN field, including our own, suggested to us that there might be co-regulatory activity and function as
part of the actions of this family of cysteine rich cytokines. CCN2 is now regarded as a major pro-fibrotic molecule acting
both down-stream and independent of TGF-β1, and appears causal in the disease afflicting multiple organs. Since diabetic renal
fibrosis is a common complication of diabetes, and a major cause of end stage renal disease (ESRD), we examined the possibility
that CCN3 (NOV), might act as an endogenous negative regulator of CCN2 with the capacity to limit the overproduction of extracellular
matrix (ECM), and thus prevent, or ameliorate fibrosis. We demonstrate, using an in vitro model of diabetic renal fibrosis,
that both exogenous treatment with CCN3 and transfection with the over-expression of the CCN3 gene in mesangial cells markedly
down-regulates CCN2 activity and blocks ECM over-accumulation stimulated by TGF-β1. Conversely, TGF-β1 treatment reduces endogenous
CCN3 expression and increases CCN2 activity and matrix accumulation, indicating an important, novel yin/yang effect. Using
the db/db mouse model of diabetic nephropathy, we confirm the expression of CCN3 in the kidney, with temporal localization
that supports these in vitro findings. In summary, the results corroborate our hypothesis that one function of CCN3 is to
regulate CCN2 activity and at the concentrations and conditions used down-regulates the effects of TGF-β1, acting to limit
ECM turnover and fibrosis in vivo. The findings suggest opportunities for novel endogenous-based therapy either by the administration,
or the upregulation of CCN3. 相似文献
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Structural basis of contraction in vertebrate smooth muscle 总被引:9,自引:0,他引:9
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Inhibition of cell expansion of excised embryonic axes of Phaseolus vulgaris was used to evaluate the growth-inhibiting activity of abscisic acid and related compounds. None of the 13 compounds tested was as active as abscisic acid. 4-Hydroxyisophorone, a substance representative of the abscisic acid ring system was essentially inactive; cis, trans-3-methylsorbic acid, a compound resembling the side chain of abscisic acid, had low activity; and cis, trans-beta-ionylideneacetic acid was one-sixth as active. Loss of the ring double bond results in a drastic decrease in biological activity. Comparison of our results with those reported previously leads to the suggestion that the double bond of the cyclohexyl moiety may have an important function in determining the degree of activity of cis, trans-ionylideneacetic acids. Two modes of action are discussed. It seems possible that the ring double bond is involved in covalent bonding in binding of the abscisic acid analogue to macromolecules. This may require formation of an intermediate epoxide. It can also be argued that stereochemical differences between cyclohexane derivatives are important factors in determining the degree of biological activity. 相似文献
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