Role of hensin in mediating the adaptation of the cortical collecting duct to metabolic acidosis.
OBJECTIVE
The cortical collecting duct is able to secrete HCO3-, a state that can be converted to acid secretion during metabolic acidosis. Bicarbonate secretion in this segment is mediated by beta-intercalated cells whereas alpha-intercalated cells perform acid secretion. During metabolic acidosis, the number of beta-intercalated cells is reduced while that of alpha-intercalated cells increases without a change in the total number of intercalated cells, suggesting conversion of one cell type to another. Using an immortalized intercalated cell line we found that this adaptation is mediated by an extracellular protein named hensin. Hensin is secreted as a monomer which is then polymerized in the extracellular environment by a complex process requiring at least three other proteins.


RESULTS
We describe that a cyclophilin, via its cis/trans prolyl isomerase activity, is required for this polymerization. This may explain the distal renal tubular acidosis observed with cyclosporin A therapy. In addition, galectin-3 is needed to aggregate the protein. Finally, we recently found that activation of integrins is also necessary for the development of the hensin fiber. Hensin is expressed in all epithelia and deletion of its gene is embryonic lethal at an early stage when the first columnar epithelia develop.


CONCLUSIONS
These studies suggest that the response of intercalated cells to metabolic acidosis uses a pathway that is involved in terminal differentiation of columnar epithelia.
Schwartz
George J
GJ
Departments of Pediatrics and Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA. george_schwartz@urmc.rochester.edu
Al-Awqati
Qais
Q
D000138:Acidosis / Q000503:physiopathology*; D000222:Adaptation, Physiological; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000503:physiopathology*; D051116:Receptors, Scavenger / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D051116:Receptors, Scavenger; C495130:hensin protein, rabbit