Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells

Wolthuis, Albert; Boes, A; Rodemann, H. Peter; Grond, J.

doi:10.1038/ki.1992.16

Cited by 66 publications

(39 citation statements)

References 29 publications

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“…This observation agrees with other reports that also directly linked the rate ofcollagen synthesis with that ofmesangial and arterial smooth muscle cell growth in culture (63)(64)(65). The in vivo relevance of these findings is evidenced by the progressive glomerulosclerosis occurring in the hypertrophied glomeruli of mice transgenic for growth hormone, where excessive deposition of ECM is closely associated with increased cell turnover (66).…”

Section: Discussionsupporting

confidence: 81%

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Riser¹,

Cortés²,

Zhao³

et al. 1992

J. Clin. Invest.

244

139

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To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (V ,), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and V was 7.68 x 103 gm3/mmHg. Total V, increment (PIP 0-150 mmHg) was 1.162 X 106 pm3 or 61% (n = 13). A 16% increase in V, was obtained over the PIP range equivalent to the pathophysiologial limits of mean transcapillary pressure difference. A similar effect of renal perfusion on V3 was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces. (J. Clin. Invest. 1992. 90:1932-1943

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Section: Discussionsupporting

confidence: 81%

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Riser¹,

Cortés²,

Zhao³

et al. 1992

J. Clin. Invest.

244

139

View full text Add to dashboard Cite

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“…3-mo-old male Wistar-Kyoto rats (WKY) were fed a standard pellet diet and water ad libitum. According to previously described methods ( 17,(19)(20)(21) Precipitation on ice was performed with 200 yd 20% trichloroacetic acid (TCA) overnight. TCA-precipitable material was pelleted by centrifugation at 2,000 g, dissolved in 0.5 M NaOH, and transferred for liquid scintillation counting.…”

Section: Methodsmentioning

confidence: 99%

“…Since a number of vasopressor hormones, such as angiotensin II, vasopressin and endothelin, also act as growth factors on vascular smooth muscle cells or MC (17,18), it was tested in the present study, whether also AP5A and AP6A stimulate growth of MC. Furthermore, both dinucleotides were tested for interactions with polypeptide growth factors.…”

Section: Introductionmentioning

confidence: 99%

Regulation of rat mesangial cell growth by diadenosine phosphates.

Heidenreich¹,

Tepel²,

Schlüter³

et al. 1995

J. Clin. Invest.

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The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (APA) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations.The growth stimulatory effect exceeded that of ATP, a,4-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insulin-like growth factor-i. To further elucidate the site of action in the cell cycle, RNA and protein synthesis were assessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cytosolic free Ca2" concentration. It is concluded that APjA and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease. (J. Clin. Invest. 1995Invest. . 95:2862Invest. -2867

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“…The supernatants were assayed for released fibronectin, while washed cell layers were sonicated in 500 /iL of 1% nonidet P-40 in PBS and assayed for cell-associated fibronectin. Fibronectin levels in all samples were determined by a double-antibody sandwich enzymelinked immunosorbent assay using the methods provided by the manufacturer (DAKO Corp, Carpinteria, Calif) and Wolthuis et al 12 A polyclonal rabbit anti-human fibronectin (1:1000) was used as the coating antibody, and the detection antibody was a peroxidase-conjugated rabbit anti-human fibronectin (1:2000).…”

Section: Measurement Of Fibronectinmentioning

confidence: 99%

Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle cell hypertrophy.

et al. 1994

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The 12-lipoxygenase pathway is a key mediator of angiotensin II (Ang II)-induced effects in the adrenal cortex. We also recently demonstrated that Ang II increases 12-and 15-lipoxygenase product levels in vascular smooth muscle cells. However, the relation between lipoxygenase activation and Ang II-induced vascular smooth muscle cell hypertrophy is not known. We studied the effects of Ang II and 12-lipoxygenase products on both total cell protein content and the levels of the matrix protein fibronectin in quiescent porcine aortic smooth muscle cells. Ang II-induced increases in cellular protein content were attenuated by the specific 12-lipoxygenase inhibitor baicalein; in contrast, the cycloxygenase inhibitor ibuprofen had no effect. Direct addition of the 12-lipoxygenase product 12-S-hydroxyeicosatetraenoic acid increased total cell protein content. We have recently shown that porcine vascular smooth muscle cell growth is potentiated in high glucose (25 mmol/L) culture conditions. We observed that both Ang II and 12-5-hydroxyeicosatetraenoic acid induced a greater increase in protein content in cells cultured for two passages in high glucose. Furthermore, Ang II and 12-5-hydroxyeicosatetraenoic acid also markedly increased fibronectin levels in cells cultured in high glucose. These results suggest that 12-lipoxygenase activation plays a key role in Ang II-induced vascular smooth muscle cell hypertrophy.

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Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells

Cited by 66 publications

References 29 publications

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Regulation of rat mesangial cell growth by diadenosine phosphates.

Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle cell hypertrophy.

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