Decreased ADAM17 expression in the lungs of a-Klotho reduced mouse

Keiko Akasaka-Manya, Hiroshi Manya*, Satomi Nadanaka, Hiroshi Kitagawa, Yoshitaka Kondo, Akihito Ishigami, Tamao Endo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The deficiency of a-Klotho in mice causes phenotypes resembling human age-associated disorders at 3–4weeks after birth and shows short lifespans of ~2months. One of the crucial symptoms is pulmonary emphysema, although a-Klotho is not expressed in the lungs. a-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 a-Klotho mouse lungs were observed, because a-Klotho is reported to have glycosidase activity. Here, we found the accumulation of heparan sulphate in the microsomal fraction of a-Klotho mouse lungs. Meanwhile, a disintegrin and metalloproteinase 17 (ADAM17) expression was decreased in a-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 a-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 a-Klotho. These may be involved in the deterioration of lung function during ageing and may be associated with the pathology of pulmonary emphysema.

Original languageEnglish
Pages (from-to)483-493
Number of pages11
JournalJournal of biochemistry
Volume167
Issue number5
DOIs
Publication statusPublished - 2020 May 1
Externally publishedYes

Keywords

  • A-Klotho
  • ADAM17
  • Ageing
  • COPD
  • Heparan sulphate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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