Renal proximal tubular cell growth and differentiation are differentially modulated by renotropic growth factors and tyrosine kinase inhibitors

Ernst, Friedlinde; Hetzel, Simone; Stracke, Sylvia; Czock, David; Vargas, Gustavo A.; Lutz, Manfred P.; Keller, Frieder; Jehle, Peter

doi:10.1046/j.1365-2362.2001.00925.x

Cited by 15 publications

(15 citation statements)

References 38 publications

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“…That IGF-1 directly induces tubular cell proliferation was indicated by evidence that PTEC highly expressed IGF-1 receptor mRNA, and exogenous IGF-1 at the concentration comparable to that produced by cultured MSC stimulated cisplatin-treated PTEC to proliferate. Our findings are in line with previous studies 36,37 showing that in vitro IGF-1 stimulated the proliferation of cultured rabbit and rat proximal tubular cells.…”

Section: Discussionsupporting

confidence: 93%

Insulin-Like Growth Factor-1 Sustains Stem Cell–Mediated Renal Repair

Imberti

Morigi

Tomasoni

et al. 2007

Journal of the American Society of Nephrology

290

241

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In mice with cisplatin-induced acute kidney injury, administration of bone marrow-derived mesenchymal stem cells (MSC) restores renal tubular structure and improves renal function, but the underlying mechanism is unclear. Here, we examined the process of kidney cell repair in co-culture experiments with MSC and cisplatin-injured proximal tubular epithelial cells (PTEC). Exposure of PTEC to cisplatin markedly reduced cell viability at 4 days, but co-culture with MSC provided a protective effect by promoting tubular cell proliferation. This effect was mediated by insulin-like growth factor-1 (IGF-1), highly expressed by MSC as mRNA and protein, since blocking the growth factor's function with a specific antibody attenuated cell proliferation of PTEC. Confirming this, knocking down IGF-1 expression in MSC by small interfering-RNA also resulted in a significant decrease in PTEC proliferation and increased apoptosis. Furthermore, in the murine model of cisplatin-induced kidney injury, administering IGF-1 gene-silenced MSC limited their protective effect on renal function and tubular structure. These findings indicate that MSC exert beneficial effects on tubular cell repair in acute kidney injury by producing the mitogenic and pro-survival factor IGF-1.

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Section: Discussionsupporting

confidence: 93%

Insulin-Like Growth Factor-1 Sustains Stem Cell–Mediated Renal Repair

Imberti

Morigi

Tomasoni

et al. 2007

Journal of the American Society of Nephrology

290

241

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“…In the present study, EGF receptor antagonist and tyrosine kinase inhibitors blocked EGF-induced inhibition of Pi uptake. This result is also supported by the report that PTCs have EGF receptor [2,3]. In PTCs, EGF-induced inhibitory effect on endothelin-1 release was also antagonized by tyrosine kinase inhibitors, consistent with a role for tyrosine kinase in the signal transduction pathway [32].…”

Section: Discussionsupporting

confidence: 83%

“…The kidney is a major site of synthesis of the EGF precursor [1] and proximal tubule cells (PTCs) also express EGF receptors [2,3]. A number of renal responses to administration of EGF have been described, including modulation of hemodynamics, renal metabolism, tubular transport functions, and eicosanoid synthesis [4].…”

Section: Introductionmentioning

confidence: 99%

Effect of Epidermal Growth Factor on Phosphate Uptake in Renal Proximal Tubule Cells: Involvement of PKC, MAPK, and cPLA<sub>2</sub>

Han

Park

Lee

et al. 2003

Kidney Blood Press Res

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Objective: The present study was conducted to examine the effect of epidermal growth factor (EGF) on Pi uptake and its related signal pathways in the primary cultured renal proximal tubule cells (PTCs). Results: EGF (50 ng/ml) inhibited Pi uptake, a typical marker of Na⁺/phosphate cotransporter, in a time- and dose-dependent manner. EGF-induced inhibition of Pi uptake was blocked by AG1478 (an EGF receptor antagonist), genistein or herbimycin A (tyrosine kinase inhibitors) and also blocked by mepacrine (a phospholipase A₂ (PLA₂) inhibitor) and AACOCF₃(a cPLA₂ inhibitor). EGF increased [³H]-arachidonic acid (AA) release, which was also blocked by AG1478, genistein or herbimycin. Furthermore, EGF-induced inhibition of Pi uptake was blocked by indomethacin (a cyclooxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not by NDGA (a lipoxygenase inhibitor). On the other hand, EGF-induced inhibition of Pi uptake was blocked by staurosporine, H-7, or bisindolylmaleimide I (PKC inhibitors), PD 98059 (a p44/42 MAPK inhibitor), but not by SB 203580 (a p38 MAPK inhibitor). EGF-induced increase of [³H]-AA release was blocked by PKC inhibitors and a p44/42 mitogen-activated protein kinase (MAPK) inhibitor, but not by a p38 MAPK inhibitor. In addition, a PKC inhibitor blocked EGF-induced phosphorylation of p44/42 MAPK. Conclusion: EGF inhibits Pi uptake via PKC-p44/42 MAPK-cPLA₂ pathway in the PTCs.

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“…[18][19][20] Apart from its beneficial effects on overall body functions, emodin has also been described in the improvement of digestion and gastrointestinal (GI) function.…”

Section: Discussionmentioning

confidence: 99%

Involvment of Endogenous Prostaglandin in Emodin-Evoked Rat Colonic Anion Secretion

Wen

Liu

et al. 2007

Biological & Pharmaceutical Bulletin

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The mammalian colon is the final station of the gastrointestinal (GI) tract, where the organism has the last opportunity to modify the electrolyte contents in the feces with balanced absorptive and secretory activities. Colonic epithelium, a typical electrolyte-transporting epithelium, lines the surface of both crypts and villi, and plays an important role in the maintenance of water and electrolyte balance.Anthraquinones are present in the roots, bark or leaves of numerous plants such as senna, cascara, aloe, frangula and rhubarb.

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Renal proximal tubular cell growth and differentiation are differentially modulated by renotropic growth factors and tyrosine kinase inhibitors

Cited by 15 publications

References 38 publications

Insulin-Like Growth Factor-1 Sustains Stem Cell–Mediated Renal Repair

Insulin-Like Growth Factor-1 Sustains Stem Cell–Mediated Renal Repair

Effect of Epidermal Growth Factor on Phosphate Uptake in Renal Proximal Tubule Cells: Involvement of PKC, MAPK, and cPLA<sub>2</sub>

Involvment of Endogenous Prostaglandin in Emodin-Evoked Rat Colonic Anion Secretion

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