title: Lipin1 Regulates Skeletal Muscle Differentiation through Extracellular Signal-regulated Kinase (ERK) Activation and Cyclin D Complex-regulated Cell Cycle Withdrawal.
abstract: Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated muscle fiber cross-sectional areas compared with wild-type mice in response to injury. Our results from a series of in vitro experiments suggest that lipin1 is up-regulated and translocated to the nucleus during myoblast differentiation and plays a key role in myogenesis by regulating the cytosolic activation of ERK1/2 to form a complex and a downstream effector cyclin D3-mediated cell cycle withdrawal. Overall, our study reveals a previously unknown role of lipin1 in skeletal muscle regeneration and expands our understanding of the cellular and molecular mechanisms underlying skeletal muscle regeneration.
authors: From the Division of Cardiovascular Medicine, Department of Internal Medicine, Saha Cardiovascular Center.
authors: Weihua
authors: W
authors: Jiang
authors: From the Division of Cardiovascular Medicine, Department of Internal Medicine, Saha Cardiovascular Center.
authors: Jing
authors: J
authors: Zhu
authors: From the Division of Cardiovascular Medicine, Department of Internal Medicine, Saha Cardiovascular Center.
authors: Xun
authors: X
authors: Zhuang
authors: Department of Physiology, University of Kentucky, Lexington, Kentucky 40536.
authors: Xiping
authors: X
authors: Zhang
authors: From the Division of Cardiovascular Medicine, Department of Internal Medicine, Saha Cardiovascular Center.
authors: Tao
authors: T
authors: Luo
authors: Department of Physiology, University of Kentucky, Lexington, Kentucky 40536.
authors: Karyn A
authors: KA
authors: Esser
authors: From the Division of Cardiovascular Medicine, Department of Internal Medicine, Saha Cardiovascular Center, hongmei.ren@uky.edu.
authors: Hongmei
authors: H
authors: Ren
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000502:physiology*; D056741:Cyclin D / Q000378:metabolism*; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology; D009687:Nuclear Proteins / Q000502:physiology*; D009929:Organ Size; D010711:Phosphatidate Phosphatase / Q000502:physiology*; D010766:Phosphorylation
chemical_list: D056741:Cyclin D; D009687:Nuclear Proteins; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6; D048049:Extracellular Signal-Regulated MAP Kinases; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase
keywords: ERK; cell cycle; lipin1; muscle regeneration; myoblast differentiation; nuclear translocation; protein phosphorylation; skeletal muscle