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PMID:19019919

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Citation

Ricono, JM, Wagner, B, Gorin, Y, Arar, M, Kazlauskas, A, Choudhury, GG and Abboud, HE (2009) PDGF receptor-{beta} modulates metanephric mesenchyme chemotaxis induced by PDGF AA. Am. J. Physiol. Renal Physiol. 296:F406-17

Abstract

PDGF B chain or PDGF receptor (PDGFR)-beta-deficient (-/-) mice lack mesangial cells. To study responses of alpha- and beta-receptor activation to PDGF ligands, metanephric mesenchymal cells (MMCs) were established from embryonic day E11.5 wild-type (+/+) and -/- mouse embryos. PDGF BB stimulated cell migration in +/+ cells, whereas PDGF AA did not. Conversely, PDGF AA was chemotactic for -/- MMCs. The mechanism by which PDGFR-beta inhibited AA-induced migration was investigated. PDGF BB, but not PDGF AA, increased intracellular Ca(2+) and the production of reactive oxygen species (ROS) in +/+ cells. Transfection of -/- MMCs with the wild-type beta-receptor restored cell migration and ROS generation in response to PDGF BB and inhibited AA-induced migration. Inhibition of Ca(2+) signaling facilitated PDGF AA-induced chemotaxis in the wild-type cells. The antioxidant N-acetyl-l-cysteine (NAC) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) abolished the BB-induced increase in intracellular Ca(2+) concentration, suggesting that ROS act as upstream mediators of Ca(2+) in suppressing PDGF AA-induced migration. These data indicate that ROS and Ca(2+) generated by active PDGFR-beta play an essential role in suppressing PDGF AA-induced migration in +/+ MMCs. During kidney development, PDGFR beta-mediated ROS generation and Ca(2+) influx suppress PDGF AA-induced chemotaxis in metanephric mesenchyme.

Links

PubMed PMC2643859 Online version:10.1152/ajprenal.90368.2008

Keywords

Animals; Calcium/metabolism; Calcium Signaling; Cells, Cultured; Chemotaxis; DNA/biosynthesis; Kidney/embryology; Mesoderm/physiology; Mice; Mice, Knockout; Phosphatidylinositol 3-Kinases/metabolism; Platelet-Derived Growth Factor/metabolism; Protein Isoforms/metabolism; Reactive Oxygen Species/metabolism; Receptor, Platelet-Derived Growth Factor alpha/metabolism; Receptor, Platelet-Derived Growth Factor beta/genetics; Receptor, Platelet-Derived Growth Factor beta/metabolism; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PDGFB

involved_in

GO:2000573: positive regulation of DNA biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFB

involved_in

GO:2000379: positive regulation of reactive oxygen species metabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFB

involved_in

GO:0050921: positive regulation of chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFB

involved_in

GO:0090280: positive regulation of calcium ion import

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFB

involved_in

GO:0035793: positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:2000573: positive regulation of DNA biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:2000379: positive regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:0050921: positive regulation of chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:0090280: positive regulation of calcium ion import

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:0035793: positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFA

involved_in

GO:0035793: positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFA

involved_in

GO:0051897: positive regulation of protein kinase B signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PDGFA

NOT|involved_in

GO:2000278: regulation of DNA biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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