DOWN-REGULATION OF THE KLOTHO GENE IN THE KIDNEY UNDER SUSTAINED CIRCULATORY STRESS IN RATS

We recently reported the isolation of the klotho gene, which is predom inantly expressed in the kidney and involved in human aging phenotypes . In our previous studies, we demonstrated that the Klotho protein or its metabolites may possibly function as humoral factor(s) and protect against endothelial dysfunction because acetylcholine-mediated NO pro duction in arteries was impaired in heterozygous klotho deficient mice (kl/+). However, the pathophysiological significance of the Klotho pr otein has not been clarified yet. In the present study, we examined ex pression of the klotho gene in the kidney of the following rat models for human diseases: (1) spontaneously hypertensive rat, (2) deoxycorti costerone acetate-salt hypertensive rat, (3) 5/6 nephrectomized rat, ( 4) non-insulin-dependent diabetes mellitus rat (the Otsuka Long-Evans Tokushima Fatty rat), and (5) rat with acute myocardial infarction. Th e expression levels of klotho mRNA in the kidney in these models were significantly lower than controls except for MI rats. This is the firs t report showing that expression of the klotho gene in the kidney is r egulated under sustained circulatory stress such as long-term hyperten sion, diabetes mellitus, and chronic renal failure. (C) 1998 Academic Press.