title: Partial deletion of the ROCK2 protein fails to reduce renal fibrosis in a unilateral ureteral obstruction model in mice.
abstract: Renal fibrosis is a well‑known cause for the progression of chronic kidney disease. Rho/Rho‑associated coiled‑coil kinase (ROCK) signaling is involved in renal fibrotic processes. Non‑selective ROCK1/2 inhibitors have been reported to reduce renal interstitial fibrosis in a rodent unilateral ureteral obstruction (UUO) model. To clarify the role and contribution of ROCK2 in renal fibrosis, the present study used ROCK2 heterozygous knockout (HKO) mice to assess collagen deposition and fibrosis‑associated gene expression in the kidney of the UUO model. In the ROCK2 HKO mice, the expression level of ROCK2 in the normal kidney was half of that in the kidney of wild‑type (WT) mice. The expression levels of ROCK1 in the ROCK2 HKO mice and WT mice were equivalent. Furthermore, in the ROCK2 HKO and the WT mice, the hydroxyproline content and the gene expression levels of collagen I and transforming growth factor‑β1 in the obstructed kidneys were augmented following UUO. By contrast, the mRNA expression of α‑smooth muscle actin decreased in the ROCK2 HKO mice, compared with that in the WT mice. The activity of ROCK in the obstructed kidneys, indicated by the phosphorylation of myosin phosphatase target subunit‑1, which is a non‑selective substrate of ROCK1 and ROCK2, was equivalent among the ROCK2 HKO and WT mice. In conclusion, no differences in renal interstitial fibrosis or UUO‑induced ROCK activity were identified between the ROCK2 HKO and WT mice, indicating that the genetic partial disruption of ROCK2 is insufficient for protecting against renal fibrosis.
authors.affiliation: Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda‑Shi, Saitama 335‑8505, Japan.
authors.forename: Itsuko
authors.initials: I
authors.lastname: Baba
authors.affiliation: Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda‑Shi, Saitama 335‑8505, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Egi
authors.affiliation: Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda‑Shi, Saitama 335‑8505, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D017353:Gene Deletion; D006579:Heterozygote; D006909:Hydroxyproline / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000473:pathology*; D008297:Male; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000201:enzymology* / Q000473:pathology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C515854:Rock1 protein, mouse; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; D006909:Hydroxyproline