title: Norcantharidin inhibits renal interstitial fibrosis by downregulating PP2Ac expression.
abstract: Norcantharidin (NCTD) has been proven to be able to attenuate renal interstitial fibrosis, but the exact molecular mechanism is still unknown. This study investigated the relationship between the anti-fibrotic effect of NCTD and its inhibition on PP2Ac expression. Here, PP2Ac was found to be positively correlated with extracellular matrix accumulation in the rat unilateral ureteral obstruction (UUO) model. Additional experiments showed that the PP2A inhibitor (okadaic acid) can ameliorate renal interstitial fibrosis by inhibiting the expression of fibronectin (FN) and collagen I (Col-I) and reversing tubular epithelial-to-mesenchymal transition in vivo and in vitro. In vitro experiments also demonstrated that ectopic over-expression of PP2Ac has a profibrotic effect in HK-2 cells. Moreover, NCTD was able to downregulate PP2Ac expression, decrease FN, Col-I, α-SMA expression, and increase E-cadherin expression in a dose-dependent manner both in vivo and in vitro. In particular, it was demonstrated that NCTD induced no evident changes in the expression of FN, Col-I, α-SMA and E-cadherin in HK-2 cells after PP2Ac was knocked down by shRNA. These results indicated that NCTD exerts an anti-fibrosis effect via inhibition of PP2Ac expression. Thus, PP2Ac could be a promising target for intervention in renal interstitial fibrosis.
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South UniversityChangsha, Hunan, PR. China; Department of Oncology, Second Xiangya Hospital, Central South UniversityChangsha, Hunan, PR. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hou
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: You
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Yi-Yun
authors.initials: YY
authors.lastname: Xi
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Duan
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Peng
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University Changsha, Hunan, PR. China.
authors.forename: Fu-You
authors.initials: FY
authors.lastname: Liu
keywords: Norcantharidin; epithelial-mesenchymal transition; protein phosphatase 2; renal interstitial fibrosis