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2020 ; 10
(1
): 2333
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TRPM7 contributes to progressive nephropathy
#MMPMID32047249
Suzuki S
; Penner R
; Fleig A
Sci Rep
2020[Feb]; 10
(1
): 2333
PMID32047249
show ga
TRPM7 belongs to the Transient Receptor Potential Melastatin family of ion
channels and is a divalent cation-conducting ion channel fused with a functional
kinase. TRPM7 plays a key role in a variety of diseases, including neuronal death
in ischemia, cancer, cardiac atrial fibrillation, malaria invasion. TRPM7 is
aberrantly over-expressed in lung, liver and heart fibrosis. It is also
overexpressed after renal ischemia-reperfusion, an event that induces kidney
injury and fibrosis. However, the role of TRPM7 in kidney fibrosis is unclear.
Using the unilateral ureteral obstruction (UUO) mouse model, we examined whether
TRPM7 contributes to progressive renal damage and fibrosis. We find that TRPM7
expression increases in UUO kidneys. Systemic application of NS8593, a known
TRPM7 inhibitor, prevents kidney atrophy in UUO kidneys, retains tubular
formation, and reduces TRPM7 expression to normal levels. Cell proliferation of
both tubular epithelial cells and interstitial cells is reduced by NS8593
treatment in UUO kidneys, as are TGF-?1/Smad signaling events. We conclude that
TRPM7 is upregulated during inflammatory renal damage and propose that
pharmacological intervention targeting TRPM7 may prove protective in progressive
kidney fibrosis.
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