SHP2-mediated signaling cascade through gp130 is essential for LIF-dependent ICaL, [Ca2+]i transient, and APD increase in cardiomyocytes

Hagiwara, Yoko; Miyoshi, Shunichiro; Fukuda, Keiichi; Nishiyama, Nobuhiro; Ikegami, Yasuyuki; Tanimoto, Kojiro; Murata, Mitsushige; Takáhashi, Eiichi; Shimoda, Kouji; Hirano, Toshio; Mitamura, Hideo; Ogawa, Satoshi

doi:10.1016/j.yjmcc.2007.09.004

Cited by 91 publications

(72 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of studies on animal ventricular cells clearly demonstrated the ability of IL-1, IL-6, and TNF-α to prolong AP duration, possibly by enhancing ICaL and inhibiting the potassium channel (38,39). Wang et al (40) reported that TNF-α downregulates in vitro IKr by impairing the function of the hERG potassium channel via the stimulation of reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of QT interval prolongation in inflammatory bowel disease

Pattanshetty

Gajulapalli

Anna

et al. 2016

Turk J Gastroenterol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Prevalence of QT interval prolongation in inflammatory bowel disease

Pattanshetty

Gajulapalli

Anna

et al. 2016

Turk J Gastroenterol

View full text Add to dashboard Cite

“…Echocardiographic analysis of MSKO hearts further demonstrated cardiac dysfunction coupled with ventricular chamber dilatation, characteristic of dilated cardiomyopathy. Molecular signaling analysis suggests that deletion of Shp2 leads to altered LIF-induced intracellular signals, including enhanced Stat3 and Erk5 activities, and impaired ] i transient and action potential duration increase in cardiomyocytes using knockin mice lacking a Shp2 docking site on gp130, a signal transducing component in LIF receptor (12). Heartspecific overexpression of Stat3 induced myocardial hypertrophy in mice, with elevated expression of ANF, ␤-myosin heavy chain, and cardiotrophin-1 genes (24).…”

Section: Discussionmentioning

confidence: 99%

Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death

Princen

Bard

Sheikh

et al. 2009

Molecular and Cellular Biology

View full text Add to dashboard Cite

The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-/ and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones.Heart failure is a serious life-threatening health problem worldwide. Numerous studies have demonstrated a link between cardiac dysfunction and insulin resistance, as well as deficiency in glucose transport (9,35,48). In the absence of manifest diabetes, insulin resistance and minor degrees of glucose intolerance are thought to be associated with and contribute to the development of nonischemic cardiomyopathy or idiopathic dilated cardiomyopathy (35,45). However, the molecular basis for this link is poorly understood.Muscle-specific gene knockout mice have presented unprecedented opportunities to decipher molecular signaling mechanisms underlying cardiomyopathic changes. Deletion of PTEN in cardiomyocytes mediated by Mck-Cre results in cardiac hypertrophy in mice (8). Dilated cardiomyopathy was also observed to various degrees in mice with conditional ablation of ErbB2 (HER2), ␤ 1 integrin, and the gp130 cytokine receptor component in the heart or muscle (16,34,37). Interestingly, despite the development of cardiomyopathy, most of these mutant mice survive to adulthood with a normal life span, suggesting limitations in their modeling of human patients' pathological processes. These mutant mouse models also show no correlation between cardiomyopathy and insulin resistance. In fact, although muscle-specific PTEN knockout mice develop cardiac hypertrophy (8), they are protected against insulin resistance and diabetes induced by high-fat diet due to enhanced insulin-stimulated glucose uptake in soleus muscle (43).Shp2 is a widely expressed cytoplasmic tyrosine phosphatase with two SH2 domains that has been implicated in signaling events downstream of receptors for growth factors, cytokines, and hormones (25, 32). In particular, Shp2 has been shown to participate in leptin and insulin signaling for the regulation of energy balance and metabolism (23...

show abstract

“…In some experiments, hAMCs were pretreated with 10 ng/mL of IL10 (Sigma I9276) or 10 ng/mL of progesterone (p7556; Sigma-Aldrich) for 2-days before the transplantation to observe the efficacy of survival of hAMCs in vivo. Enzymatically isolated EGFP-positive cardiomyocytes 20,21 were selected by glass pipette driven by a manipulator mounted on the inverted fluorescent microscope, then used for the FISH experiment to determine the origin of EGFP-positive transdifferentiated cardiomyocytes. See also the Online Data Supplement.…”

Section: Model In Vivomentioning

confidence: 99%

Xenografted Human Amniotic Membrane–Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes

Tsuji¹,

Miyoshi²,

Ikegami³

et al. 2010

Circulation Research

Self Cite

170

165

View full text Add to dashboard Cite

Key Words: cardiomyogenesis Ⅲ human mesenchymal stem cell Ⅲ immunologic tolerance Ⅲ myocardial infarction Ⅲ cell-based therapy A lthough embryonic stem cells 1 and induced pluripotent stem (iPS) cells 2 can be differentiated into cells of various organs, including cardiomyocytes, there are many underlining problems to overcome before clinical applications can be used, eg, tumorigenicity. 3 Autografts of iPS cells may not cause immunologic rejection; ironically, however, possible neoplasm formation would cause a serious problem because the neoplasm would not be rejected by the withdrawal of immunosuppressive agents. On the other hand, mesenchymal stem cells (MSCs) have recently been used for clinical application, and their safety and feasibility in cardiac stem cell-based therapy have been demonstrated. 4 Thus, MSCs are a more important cellular source for stem cell-based therapy from a practical point of view.The efficacy of human bone marrow-derived MSCs (BMMSCs) was still limited, 5 however, because of low efficiency for cardiomyogenic transdifferentiation. 6 We previously reported that non-marrow-derived mesenchymal cells had higher cardiomyogenic transdifferentiation efficiency, eg, menstrual blood-derived mesenchymal cells (MMCs), 7 umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), 8 and placental chorionic plate-derived mesenchymal cells (PCPCs). 9 These cells are thought to be used by an allograft; therefore, problems of immunologic rejection arise. However, an allograft may be superior to an autograft in several ways. Taking into account the background condition of the patient (eg, metabolic disease or age), Original received July 16, 2009; revision received April 14, 2010; accepted April 22, 2010 16 reported significant recovery of cardiac function by the rat amnion-derived cell transplantation in rat myocardial infarction (MI) model, however, they failed to show clear evidence of cardiomyogenic differentiation in vivo. Therefore, in the present study, we attempted to show: (1) the powerful cardiomyogenic transdifferentiation potential of our isolated hAMCs, and the beneficial effect of transplantation of hAMCs on cardiac function in vivo; (2) the induction of immunologic tolerance so that hAMCs can be a powerful allograftable stem cell source without either the administration of immunosuppressive agents or matching of MHC typing; (3) the mechanism of induction of tolerance; and (4) the close relationship between the cardiomyogenic transdifferentiation of mesenchymal cells and the process of immunologic tolerance. MethodsAn expanded Methods section is available in the Online Data Supplement at http://circres.ahajournals.org. Isolation and Culture of Human Amniotic Membrane-Derived Mesenchymal CellsHuman amniotic membrane was collected, with informed consent from individual patients, after delivery of a male neonate. The study was approved by the ethics committee of Keio University School of Medicine. The precise methods for culture have been described previously. 9,17 Detail is shown in...

show abstract

SHP2-mediated signaling cascade through gp130 is essential for LIF-dependent ICaL, [Ca2+]i transient, and APD increase in cardiomyocytes

Cited by 91 publications

References 24 publications

Prevalence of QT interval prolongation in inflammatory bowel disease

Prevalence of QT interval prolongation in inflammatory bowel disease

Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death

Xenografted Human Amniotic Membrane–Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes

Contact Info

Product

Resources

About