title: Knockdown of RTN1A attenuates ER stress and kidney injury in albumin overload-induced nephropathy.
abstract: Our previous studies have suggested a critical role of reticulon (RTN)1A in mediating endoplasmic reticulum (ER) stress in kidney cells of animal models and humans with kidney diseases. A large body of evidence suggests that proteinuria itself can cause tubular cell injury leading to the progression of kidney disease. In the present study, we determined whether RTN1A mediates proteinuria-induced tubular cell injury through increased ER stress. We found that incubation of HK2 cells with human serum albumin induced the expression of RTN1A and ER stress markers, whereas knockdown of RTN1A expression attenuated human serum albumin-induced ER stress and tubular cell apoptosis in vitro. In vivo, we found that tubular cell-specific RTN1 knockdown resulted in a significant attenuation of tubular cell ER stress, apoptosis, and renal fibrosis in a model of albumin overload nephropathy. Based on these findings, we conclude that RTN1A is a key mediator for proteinuria-induced tubular cell toxicity and renal fibrosis.
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; and Department of Nephrology, Shanghai Six Municipal Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China cijiang.he@mssm.edu.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; and Department of Nephrology, Shanghai Six Municipal Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Nephrology, Shanghai Six Municipal Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Kyung
authors.initials: K
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
mesh_terms: D000419:Albuminuria / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005355:Fibrosis; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012709:Serum Albumin / Q000633:toxicity*; D012710:Serum Albumin, Bovine; D000075462:Serum Albumin, Human; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: C422455:ALB protein, human; D009419:Nerve Tissue Proteins; C081781:RTN1 protein, human; C489914:Rtn1 protein, mouse; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D000075462:Serum Albumin, Human
keywords: apoptosis; endoplasmic reticulum stress; kidney disease; proteinuria; renal tubular cells; reticulon-1