title: Transcription Factor Trps1 Promotes Tubular Cell Proliferation after Ischemia-Reperfusion Injury through cAMP-Specific 3',5'-Cyclic Phosphodiesterase 4D and AKT.
abstract: Trichorhinophalangeal 1 (Trps1) is a transcription factor essential for epithelial cell morphogenesis during kidney development, but the role of Trps1 in AKI induced by ischemia-reperfusion (I/R) remains unclear. Our study investigated Trps1 expression during kidney repair after acute I/R in rats and explored the molecular mechanisms by which Trps1 promotes renal tubular epithelial cell proliferation. Trps1 expression positively associated with the extent of renal repair after I/R injury. Compared with wild-type rats, rats with knockdown of Trps1 exhibited significantly delayed renal repair in the moderate I/R model, with lower GFR levels and more severe morphologic injury, whereas rats overexpressing Trps1 exhibited significantly accelerated renal repair after severe I/R injury. Additionally, knockdown of Trps1 inhibited and overexpression of Trps1 enhanced the proliferation of renal tubular epithelial cells in rats. Chromatin immunoprecipitation sequencing assays and RT-PCR revealed that Trps1 regulated cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d) expression. Knockdown of Trps1 decreased the renal protein expression of Pde4d and phosphorylated Akt in rats, and dual luciferase analysis showed that Trps1 directly activated Pde4d transcription. Furthermore, knockdown of Pde4d or treatment with the phosphatidylinositol 3 kinase inhibitor wortmannin significantly inhibited Trps1-induced tubular cell proliferation in vitro Trps1 may promote tubular cell proliferation through the Pde4d/phosphatidylinositol 3 kinase/AKT signaling pathway, suggesting Trps1 as a potential therapeutic target for kidney repair after I/R injury.
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ju-Rong
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Chen
authors.initials: C
authors.lastname: Ke-Hong
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Huang
authors.initials: H
authors.lastname: Kun
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Fu
authors.initials: F
authors.lastname: Bi-Qiong
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Lin
authors.initials: L
authors.lastname: Li-Rong
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jian-Guo
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and.
authors.forename: Li
authors.initials: L
authors.lastname: Kai-Long
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China; and heynmail@163.com.|Department of Nephrology, People's Liberation Army of China General Hospital, Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Ya-Ni
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology* / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C095813:Pde4a protein, mouse
keywords: Pde4d; Trps1; injury; ischemia-reperfusion; proliferation; renal tubule epithelial cell