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TRPC6 inactivation does not protect against diabetic kidney disease in streptozotocin (STZ)-treated Sprague-Dawley rats.

ABSTRACT: Canonical transient receptor potential-6 (TRPC6) channels have been implicated in the progression of several forms of kidney disease (1). While there is strong evidence that glomerular TRPC6 channels are dysregulated in diabetic nephropathy (DN), there is no consensus as to whether deletion or inactivation of TRPC6 is protective in animal models of DN. A previous study in Dahl salt-sensitive rats suggests that TRPC6 knockout has a modest protective effect in streptozotocin (STZ)-induced DN (2). In the present study, we examined whether inactivation of TRPC6 channels by CRISPR/Cas9 editing (Trpc6 del/del rats) affects progression of STZ-induced DN in Sprague-Dawley rats. Wild-type littermates (Trpc6 wt/wt rats) were used as controls. We observed that a single injection of STZ resulted in severe hyperglycemia that was sustained over a 10-week period, accompanied by a marked reduction in circulating C-peptide, dyslipidemia, and failure to gain weight compared to vehicle-treated animals. Those effects were equally severe in Trpc6 wt/wt and Trpc6 del/del rats. STZ treatment resulted in increased urine albumin excretion at 4, 8, and 10 weeks after injection, and this effect was equally severe in Trpc6 wt/wt and Trpc6 del/del rats. TRPC6 inactivation had no effect on blood urea nitrogen (BUN), plasma creatinine concentration, urine nephrin excretion, or kidney weight:body weight ratio measured 10 weeks after STZ injection. STZ treatment evoked modest and equivalent mesangial expansion in Trpc6 wt/wt and Trpc6 del/del rats. In summary, we observed no protective effect of TRPC6 inactivation on STZ-induced DN in rats on the Sprague-Dawley background.

SUBMITTER: Hassanzadeh Khayyat N 

PROVIDER: S-EPMC6996301 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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