title: RTN1 mediates progression of kidney disease by inducing ER stress.
abstract: Identification of new biomarkers and drug targets for chronic kidney disease (CKD) is required for the development of more effective therapy. Here we report an association between expression of reticulon 1 (RTN1) and severity of CKD. An isoform-specific increase in the expression of RTN1A is detected in the diseased kidneys from mice and humans, and correlates inversely with renal function in patients with diabetic nephropathy. RTN1 overexpression in renal cells induces ER stress and apoptosis, whereas RTN1 knockdown attenuates tunicamycin-induced and hyperglycaemia-induced ER stress and apoptosis. RTN1A interacts with PERK through its N-terminal and C-terminal domains, and mutation of these domains prevents this effect on ER stress. Knockdown of Rtn1a expression in vivo attenuates ER stress and renal fibrosis in mice with unilateral ureteral obstruction, and also attenuates ER stress, proteinuria, glomerular hypertrophy and mesangial expansion in diabetic mice. Together, these data indicate that RTN1A contributes to progression of kidney disease by inducing ER stress.
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.|Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.|Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
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 10029, USA.
authors.forename: Zhengzhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
authors.forename: Xuezhu
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.affiliation: Division of Nephrology, Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Jim
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.affiliation: Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
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 10029, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: He
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D005260:Female; D055879:Gene Knock-In Techniques; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014517:Ureteral Obstruction / Q000150:complications; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D019892:eIF-2 Kinase; C081781:RTN1 protein, human; C489914:Rtn1 protein, mouse