Abstract: TH-OR079

Cadherin-11 Is Induced by BMP7 and Stimulates Cap Mesenchyme Formation

Session Information

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology

Authors

  • Awazu, Midori, Keio University School of Medicine, Tokyo, Japan
  • Nagata, Michio, University of Tsukuba , Tsukuba, Ibaraki, Japan
  • Hida, Mariko, Keio University School of Medicine, Tokyo, Japan
Background

Cadherin-11 (CDH11) is an adhesion molecule specific to mesenchymal cells, which has been shown to promote cell migration and compaction and be involved in the differentiation of progenitor cells. In the developing kidney, CDH11 is expressed in cap mesenchyme and the interstitium. We investigated the role of CDH11 in kidney development and its relationship to BMP7, a growth factor necessary for maintaining and priming nephron progenitors.

Methods

Mice embryonic day 12 (E12) and E13 kidneys were transfected with two different siRNA against CDH11 (a or b) or irrelevant siRNA and cultured. Ureteric bud and cap mesenchyme were stained with pancytokeratin and Six2, respectively. An immortalized metanephric mesenchymal cell line MS7 was generated from the metanephroi of E11.5 homozygous mouse transgenic for H-2Kb-tsA (J Am Soc Nephrol 12:964, 2001). The effect of different concentrations of BMP7 (0.25, 1, and 10 nM) on CDH11 expression in MS7 was assessed by quantitative real-time PCR and immunoblot.

Results

Cap mesenchyme, marked by Six2, was well observed around ureteric tips in control metanephroi and those transfected with irrelevant siRNA. In metanephroi transfected with siRNA a or b, on the other hand, Six2-positive cells were diffusely distributed and condensation around the ureteric tips was faint. CDH11 expression, assessed by whole mount staining, was distinctly observed in cap mesenchyme in controls, but was diffuse and reduced in metanephroi transfected with siRNAs. Ureteric bud tip number was significantly reduced by siRNAs (a 6.3±1.5, b 5.8±0.2) compared with controls (7.3±2.4/kidney). Kidney size cultured with siRNAs also tended to be smaller (a 6.3±1.5, b 5.8±0.2, control 7.3±2.4). Incubation of MS7 with BMP7 for 24 h dose-dependently increased mRNA and protein expression of CDH11 with the maximal effect at 1 nM. Cadherin 6 and E-cadherin were not expressed by MS7 nor induced by BMP7. As previously reported by us, BMP7 1 nM stimulated both ERK and p38 at 24 h. While BMP7-stimulated proliferation of MS7 was suppressed by a MEK inhibitor PD98059 5 µM or a p38 inhibitor SB203580, BMP7-induced CDH11 expression was not inhibited by PD98059 or SB203580 alone but by combination of both.

Conclusion

CDH11 is induced by BMP7 via ERK and p38, and stimulates cap mesenchyme formation.

Funding

  • Government Support - Non-U.S.