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Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0032617 (
polyuria
)
3,056
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A main feature of Fabry disease is nephropathy, with
polyuria
an early manifestation; however, the mechanism that underlies
polyuria
and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Gla
tm
mice with transgenic mice that expressed human Gb3 synthase (
A4GALT
) and generated the Gla
tm
Tg(CAG-
A4GALT
) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit
polyuria
and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of
polyuria
and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure ( i.e., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules-Na
+
-K
+
-ATPase, uromodulin, and Na
+
-K
+
-2Cl
-
cotransporter-that are involved in Na
+
reabsorption in mTALs and the associated loss of urine-concentrating ability resulted in progressive water- and salt-loss phenotypes. Gla
tm
Tg(CAG-
A4GALT
) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes
polyuria
and renal impairment and contributes to the pathophysiology of Fabry nephropathy.-Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the Gla
tm
Tg(CAG-
A4GALT
) Fabry model mice.
...
PMID:Medullary thick ascending limb impairment in the Gla
tm
Tg(CAG-A4GALT) Fabry model mice. 2955 30
