Abstract: TH-PO370

K-Cadherin Protein Transfer from Proximal to Distal Tubule Cells Is Associated with the Release of BMP-7

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Authors

  • Kalsi, Kameljit Kaur, South West Thames Institute for Renal Research, London, United Kingdom
  • Jain, Seema, South West Thames Institute for Renal Research, London, United Kingdom
  • Phanish, Mysore Keshavmurthy, SW Thames renal and transplantation unit, London, United Kingdom
  • Dockrell, Mark E., South West Thames Institute for Renal Research, London, United Kingdom
Background

Cadherins are structural trans-membrane proteins that maintain the epithelial integrity by homodimerization. In the human kidney K-Cadherin (CDH6) is exclusively expressed in proximal tubular epithelial cells (PTEC) as opposed to the mouse, where K-Cadherin is only expressed in embryonic tubular cells. K-Cadherin exhibits low homology to N-(38%) & E-cadherin (35%) and the loss of K-Cadherin is associated with progression of kidney disease. Loss of K-Cadherin could suggest that it is a signal of proximal tubular damage and is involved in intercellular signalling between proximal and distal cells within the kidney which may prevent progression of epithelial remodelling.

Methods

Tissue from 3 months post-transplant human biopsies was probed for K-Cadherin by immunohistochemistry. Epithelial cells from mice kidneys were separated into predominantly distal and proximal fractions and cultured to confluence. Conditioned human PTEC media taken from confluent PTEC cells was added to mice cells, allowed to incubate for 24h; cells treated with conditioned media were compared to cells treated with control media. Media was collected and cells were lysed for western blot analysis.

Results

Analysis of human biopsy tissue identified vesicular K-Cadherin in distal tubules (in addition to membrane staining identified in proximal tubules). We identified the presence of full length K-Cadherin in the medium of primary human (PTEC) cultures and investigated the effects of conditioned media from human PTEC on mice distal or proximal tubular epithelial cells. De novo K-Cadherin expression was detected (p<0.05, n=3) in distal mice cells treated with PTEC media compared to treatment with control media, K-cadherin in mice proximal cells (megalin positive) treated with PTEC media was not as pronounced. Expression of the kidney specific cadherin (ksp-cadherin, CDH16) followed the same pattern. Media was analysed for the distal anti-fibrotic factor Bone Morphogenetic Protein 7 (BMP7) release from distal and proximal tubular cells treated with PTEC media, both were positive for BMP7 compared to treatment with control media.

Conclusion

Release of K-cadherin from PTECs is incorporated into distal cells is associated with BMP-7 secretion, possibly enhancing epithelial integrity and may represent a previously unrecognised trans-nephron communication.

Funding

  • Private Foundation Support