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Role of a RhoA/ROCK-dependent pathway on renal connexin43 regulation in the angiotensin ii-induced renal damage

dc.contributor.authorGómez G.I.
dc.contributor.authorVelarde V.
dc.contributor.authorSáez J.C.
dc.date.accessioned2020-09-02T22:19:53Z
dc.date.available2020-09-02T22:19:53Z
dc.date.issued2019
dc.identifier10.3390/ijms20184408
dc.identifier.citation20, 18, -
dc.identifier.issn16616596
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4795
dc.descriptionIn various models of chronic kidney disease, the amount and localization of Cx43 in the nephron is known to increase, but the intracellular pathways that regulate these changes have not been identified. Therefore, we proposed that: “In the model of renal damage induced by infusion of angiotensin II (AngII), a RhoA/ROCK-dependent pathway, is activated and regulates the abundance of renal Cx43". In rats, we evaluated: 1) the time-point where the renal damage induced by AngII is no longer reversible; and 2) the involvement of a RhoA/ROCK-dependent pathway and its relationship with the amount of Cx43 in this irreversible stage. Systolic blood pressure (SBP) and renal function (urinary protein/urinary creatinine: Uprot/UCrea) were evaluated as systemic and organ outcomes, respectively. In kidney tissue, we also evaluated: 1) oxidative stress (amount of thiobarbituric acid reactive species), 2) inflammation (immunoperoxidase detection of the inflammatory markers ED-1 and IL-1β), 3) fibrosis (immune detection of type III collagen; Col III) and 4) activity of RhoA/ROCK (amount of phosphorylated MYPT1; p-MYPT1). The ratio Uprot/UCrea, SBP, oxidative stress, inflammation, amount of Cx43 and p-MYPT1 remained high 2 weeks after suspending AngII treatment in rats treated for 4 weeks with AngII. These responses were not observed in rats treated with AngII for less than 4 weeks, in which all measurements returned spontaneously close to the control values after suspending AngII treatment. Rats treated with AngII for 6 weeks and co-treated for the last 4 weeks with Fasudil, an inhibitor of ROCK, showed high SBP but did not present renal damage or increased amount of renal Cx43. Therefore, renal damage induced by AngII correlates with the activation of RhoA/ROCK and the increase in Cx43 amounts and can be prevented by inhibitors of this pathway. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
dc.language.isoen
dc.publisherMDPI AG
dc.subjectCx43
dc.subjectFasudil
dc.subjectFibrosis
dc.subjectHypertensive nephropathy
dc.subjectInflammation
dc.subjectOxidative stress
dc.subjectalpha tubulin
dc.subjectangiotensin II
dc.subjectCD68 antigen
dc.subjectcollagen type 3
dc.subjectcollagen type 4
dc.subjectconnexin 43
dc.subjectcreatinine
dc.subjectfasudil
dc.subjectinterleukin 1beta
dc.subjectmypt1 protein
dc.subjectpeptides and proteins
dc.subjectprotein
dc.subjectRho kinase
dc.subjectRhoA guanine nucleotide binding protein
dc.subjectthiobarbituric acid reactive substance
dc.subjectunclassified drug
dc.subject1 (5 isoquinolinesulfonyl) 2 methylpiperazine
dc.subjectangiotensin II
dc.subjectconnexin 43
dc.subjectcreatinine
dc.subjectfasudil
dc.subjectGJA1 protein, mouse
dc.subjectRho kinase
dc.subjectRhoA guanine nucleotide binding protein
dc.subjectRhoA protein, mouse
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectclinical evaluation
dc.subjectclinical outcome
dc.subjectcontrolled study
dc.subjectcorrelation function
dc.subjectcreatinine urine level
dc.subjectenzyme activation
dc.subjectenzyme activity
dc.subjecthistopathology
dc.subjectimmunoperoxidase staining
dc.subjectinflammation
dc.subjectkidney fibrosis
dc.subjectkidney function
dc.subjectkidney injury
dc.subjectkidney tissue
dc.subjectmale
dc.subjectnonhuman
dc.subjectoxidative stress
dc.subjectprotein phosphorylation
dc.subjectprotein urine level
dc.subjectrat
dc.subjectregulatory mechanism
dc.subjectrenal protection
dc.subjectsignal transduction
dc.subjectsystolic blood pressure
dc.subjectanimal
dc.subjectdisease model
dc.subjectgene expression regulation
dc.subjectkidney disease
dc.subjectmetabolism
dc.subjectsignal transduction
dc.subjecttime factor
dc.subjecturine
dc.subject1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
dc.subjectAngiotensin II
dc.subjectAnimals
dc.subjectConnexin 43
dc.subjectCreatinine
dc.subjectDisease Models, Animal
dc.subjectGene Expression Regulation
dc.subjectKidney Diseases
dc.subjectMale
dc.subjectOxidative Stress
dc.subjectRats
dc.subjectrho-Associated Kinases
dc.subjectrhoA GTP-Binding Protein
dc.subjectSignal Transduction
dc.subjectTime Factors
dc.titleRole of a RhoA/ROCK-dependent pathway on renal connexin43 regulation in the angiotensin ii-induced renal damage
dc.typeArticle


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