In:
The Journal of Biochemistry, Oxford University Press (OUP), Vol. 167, No. 5 ( 2020-05-01), p. 483-493
Abstract:
The deficiency of α-Klotho in mice causes phenotypes resembling human age-associated disorders at 3–4 weeks after birth and shows short lifespans of ∼2 months. One of the crucial symptoms is pulmonary emphysema, although α-Klotho is not expressed in the lungs. α-Klotho secreted from the kidneys is probably involved in the pathology of emphysema because kidney-specific knockout mice exhibit emphysematous structural changes. We examined whether any glycan changes in α-Klotho mouse lungs were observed, because α-Klotho is reported to have glycosidase activity. Here, we found the accumulation of heparan sulphate in the microsomal fraction of α-Klotho mouse lungs. Meanwhile, a disintegrin and metalloproteinase 17 (ADAM17) expression was decreased in α-Klotho mice. From these results, it is thought that the increase in heparan sulphate is due to insufficient cleavage of the core protein by ADAM17. Additionally, a reduction in α-Klotho and a decline of ADAM17 were also observed both in normal aged mice and in senescence marker protein-30 (SMP30) knockout mice, a mouse model of premature ageing. Thus, the decrease in ADAM17 is caused by the reduction in α-Klotho. These may be involved in the deterioration of lung function during ageing and may be associated with the pathology of pulmonary emphysema.
Type of Medium:
Online Resource
ISSN:
0021-924X
,
1756-2651
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2009977-0
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