Essential Roles of an Intercalated Disc Protein, mXinβ, in Postnatal Heart Growth and Survival
| Autor: | Thomas D. Scholz, Han Zhong Feng, Cheng I. Lin, Elisabeth A. Gustafson-Wagner, Fu Chi Chan, Jian Ping Jin, Jim J.-C. Lin, Jenny Li-Chun Lin, Baoli Yang, Benjamin E. Reinking, Qinchuan Wang |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Cell Survival Physiology Heart growth medicine.medical_treatment Cardiomyopathy Article Mice Downregulation and upregulation Internal medicine medicine Animals symbols.heraldic_charge STAT3 Protein kinase B Cell Proliferation Mice Knockout biology Growth factor Heart shape Nuclear Proteins Heart LIM Domain Proteins medicine.disease DNA-Binding Proteins Mice Inbred C57BL Cytoskeletal Proteins Endocrinology medicine.anatomical_structure Animals Newborn biology.protein symbols Cardiology and Cardiovascular Medicine Intercalated disc |
| Zdroj: | Circulation Research. 106:1468-1478 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Rationale : The Xin repeat–containing proteins mXinα and mXinβ localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinα directly interacts with β-catenin, p120-catenin, and actin filaments. Ablation of mXin α results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinβ in mXinα-deficient hearts suggests a partial compensation. Objective : The essential roles of mXinβ in cardiac development and intercalated disc maturation were investigated. Methods and Results : Ablation of mXin β led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinα. Postnatal upregulation of mXinβ in wild-type hearts, as well as altered apoptosis and proliferation in mXin β-null hearts, suggests that mXinβ is required for postnatal heart remodeling. The mXin β-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinβ resulted in the failure of forming mature intercalated discs and the mislocalization of mXinα and N-cadherin. The mXin β-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal-regulated kinases 1 and 2. Conclusions : These findings identify not only an essential role of mXinβ in the intercalated disc maturation but also mechanisms of mXinβ modulating N-cadherin–mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival. |
| Databáze: | OpenAIRE |
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