title: miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy.
abstract: How the kidney responds to the metabolic cues from the environment remains a central question in kidney research. This question is particularly relevant to the pathogenesis of diabetic nephropathy (DN) in which evidence suggests that metabolic events in podocytes regulate chromatin structure. Here, we show that miR-93 is a critical metabolic/epigenetic switch in the diabetic milieu linking the metabolic state to chromatin remodelling. Mice with inducible overexpression of a miR-93 transgene exclusively in podocytes exhibit significant improvements in key features of DN. We identify miR-93 as a regulator of nucleosomal dynamics in podocytes. miR-93 has a critical role in chromatin reorganization and progression of DN by modulating its target Msk2, a histone kinase, and its substrate H3S10. These findings implicate a central role for miR-93 in high glucose-induced chromatin remodelling in the kidney, and provide evidence for a previously unrecognized role for Msk2 as a target for DN therapy.
authors.affiliation: Section of Nephrology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1468, Houston, Texas 77030, USA.|Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Shawn S
authors.identifier: 0000-0001-6090-9505
authors.initials: SS
authors.lastname: Badal
authors.affiliation: Section of Nephrology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1468, Houston, Texas 77030, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section of Nephrology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1468, Houston, Texas 77030, USA.
authors.forename: Jianyin
authors.initials: J
authors.lastname: Long
authors.affiliation: Center for Genomic and Computational Biology, Duke University, 101 Science Drive, Durham, North Carolina 27708, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Corcoran
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Benny H
authors.initials: BH
authors.lastname: Chang
authors.affiliation: Department of Pathology and Molecular Medicine, Houston Methodist Hospital, 6565 Fannin Street, Houston, Texas 77030, USA.
authors.forename: Luan D
authors.initials: LD
authors.lastname: Truong
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Yashpal S
authors.initials: YS
authors.lastname: Kanwar
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Overbeek
authors.affiliation: Section of Nephrology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1468, Houston, Texas 77030, USA.|Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.|Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Farhad R
authors.initials: FR
authors.lastname: Danesh
mesh_terms: D000368:Aged; D000818:Animals; D042002:Chromatin Assembly and Disassembly; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C551470:Mirn93 microRNA, mouse; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C485459:Rps6ka4 protein, mouse