RGD Reference Report - Protective role of Trpc6 knockout in the progression of diabetic kidney disease. - Rat Genome Database

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Protective role of Trpc6 knockout in the progression of diabetic kidney disease.

Authors: Spires, Denisha  Ilatovskaya, Daria V  Levchenko, Vladislav  North, Paula E  Geurts, Aron M  Palygin, Oleg  Staruschenko, Alexander 
Citation: Spires D, etal., Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F1091-F1097. doi: 10.1152/ajprenal.00155.2018. Epub 2018 Jun 20.
RGD ID: 149735534
Pubmed: PMID:29923767   (View Abstract at PubMed)
PMCID: PMC6230750   (View Article at PubMed Central)
DOI: DOI:10.1152/ajprenal.00155.2018   (Journal Full-text)

Diabetic kidney disease (DKD) is a chronic kidney pathology that leads to end-stage renal disease. Previous studies from our laboratory indicate that there is an association between the development of DKD and the transient receptor potential canonical 6 (TRPC6) channel. Trpc6 expression and activity were increased in the streptozotocin (STZ)-treated Dahl Salt-sensitive (Dahl SS) rat, an established model of type 1 diabetes. Here, using a Trpc6 knockout created on the Dahl SS rat background (SSTrpc6-/-), we test the hypothesis that the absence of Trpc6 will protect podocytes and kidney function during the development of DKD. Four groups of animals (control SSWT, SSTrpc6-/-, STZ-treated SSWT, and STZ-SSTrpc6-/-) were utilized in this study. Diabetes development was monitored for 11 wk after STZ injection with periodic weight, glucose, and urinary output measurements. There was an increase in albuminuria and glomerular injury following STZ treatment, which was not different between Dahl SS and SSTrpc6-/- groups. Western blot analysis revealed elevated levels of nephrin in urine samples of STZ-SSWT rats, which was higher compared with STZ-SSTrpc6-/- rats. Furthermore, pathological increases in basal [Ca2+]i levels and foot process damage of podocytes during the development of DKD was attenuated in the STZ-SSTrpc6-/- compared with STZ-SSWT rats. Overall, our data indicate that TRPC6 channel inhibition may have at least partial renoprotective effects, which could lead to the development of new pharmacological tools to treat or prevent the progression of DKD.



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Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SS-Trpc6em1McwiRatdecreased body weight inducesIMPinsulin and streptozotocincompared to wild type and SS-Trpc6em1Mcwi vehicle-treated controlRGD 
SS/JrHsdMcwiRatdecreased body weight inducesIAGPinsulin and streptozotocincompared to wild type and SS-Trpc6em1Mcwi vehicle-treated controlRGD 
Trpc6Ratdecreased body weight inducesIMPinsulin and streptozotocincompared to wild type and SS-Trpc6em1Mcwi vehicle-treated controlRGD 
Trpc6em1McwiRatdecreased body weight inducesIMPinsulin and streptozotocincompared to wild type and SS-Trpc6em1Mcwi vehicle-treated controlRGD 
SS-Trpc6em1McwiRatdecreased creatinine clearance inducesIMPinsulin and streptozotocincompared to STZ-treated wild typeRGD 
Trpc6Ratdecreased creatinine clearance inducesIMPinsulin and streptozotocincompared to STZ-treated wild typeRGD 
Trpc6em1McwiRatdecreased creatinine clearance inducesIMPinsulin and streptozotocincompared to STZ-treated wild typeRGD 
SS-Trpc6em1McwiRatglomerulosclerosis inducesIMPinsulin and streptozotocincompared to wild type vehicle-treated controlRGD 
SS/JrHsdMcwiRatglomerulosclerosis inducesIAGPinsulin and streptozotocincompared to wild type vehicle-treated controlRGD 
Trpc6Ratglomerulosclerosis inducesIMPinsulin and streptozotocincompared to wild type vehicle-treated controlRGD 
Trpc6em1McwiRatglomerulosclerosis inducesIMPinsulin and streptozotocincompared to wild type vehicle-treated controlRGD 
SS/JrHsdMcwiRatincreased body weight inducesIAGPinsulin and streptozotocincompared to wild type and SS-Trpc6em1Mcwi vehicle-treated controlRGD 
SS-Trpc6em1McwiRatincreased circulating glucose level inducesIMPinsulin and streptozotocincompared to vehicle-treated wild type and controlRGD 
Trpc6Ratincreased circulating glucose level inducesIMPinsulin and streptozotocincompared to vehicle-treated wild type and controlRGD 
Trpc6em1McwiRatincreased circulating glucose level inducesIMPinsulin and streptozotocincompared to vehicle-treated wild type and controlRGD 
SS/JrHsdMcwiRatincreased creatinine clearance inducesIAGPinsulin and streptozotocincompared to wild type and SS-Trpc6em1McwiRGD 
SS-Trpc6em1McwiRatincreased urine flow rate inducesIMPinsulin and streptozotocincompared to vehicle-treated wild type and controlRGD 
SS/JrHsdMcwiRatincreased urine flow rate inducesIAGPinsulin and streptozotocincompared to wild type and SS-Trpc6em1Mcwi vehicle-treated controlRGD 
Trpc6Ratincreased urine flow rate inducesIMPinsulin and streptozotocincompared to vehicle-treated wild type and controlRGD 
Trpc6em1McwiRatincreased urine flow rate inducesIMPinsulin and streptozotocincompared to vehicle-treated wild type and controlRGD 
SS-Trpc6em1McwiRatincreased urine microalbumin level inducesIMPinsulin and streptozotocincompared to vehicle-treated controlRGD 
SS/JrHsdMcwiRatincreased urine microalbumin level inducesIAGPinsulin and streptozotocincompared to vehicle-treated controlRGD 
Trpc6Ratincreased urine microalbumin level inducesIMPinsulin and streptozotocincompared to vehicle-treated controlRGD 
Trpc6em1McwiRatincreased urine microalbumin level inducesIMPinsulin and streptozotocincompared to vehicle-treated controlRGD 
SS/JrHsdMcwiRatpodocyte foot process effacement inducesIAGPinsulin and streptozotocincompared to control and STZ treated SS-Trpc6em1McwiRGD 
Objects Annotated

Genes (Rattus norvegicus)
Trpc6  (transient receptor potential cation channel, subfamily C, member 6)
Trpc6em1Mcwi  (transient receptor potential cation channel, subfamily C, member 6; CRISPR/Cas9 induced mutant 1, Medical College of Wisconsin)

Genes (Mus musculus)
Trpc6  (transient receptor potential cation channel, subfamily C, member 6)

Genes (Homo sapiens)
TRPC6  (transient receptor potential cation channel subfamily C member 6)

Strains
SS-Trpc6em1Mcwi  (NA)
SS/JrHsdMcwi  (NA)


Additional Information