Endostatin stimulates proliferation and migration of adult rat cardiac fibroblasts through PI3K/Akt pathway

Okada, Muneyoshi; Oba, Yoko; Yamawaki, Hideyuki

doi:10.1016/j.ejphar.2015.01.019

Cited by 40 publications

(34 citation statements)

References 31 publications

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“…MacLean J reported that JNK and AKT were implicated in activating phenoconversion of human heart fibroblasts [35]. But, Okada M reported that Endostatin stimulated proliferation and migration of adult rat cardiac fibroblasts through Akt pathway, not ERK, JNK and p38 MAPK [36]. In this present work, we found that both AKT and ERK took part in expression of Ki67 and FAP in CCD-18Co cells regulated by PGRN, but not JNK and p38.…”

Section: Discussioncontrasting

confidence: 47%

Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal cancer

et al. 2017

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Cancer associated fibroblasts (CAFs) are a crucial cellular component in tumor microenvironment and could promote tumor progression. CAFs are usually derived from resident fibroblasts, which undergoing an activated process stimulated by tumor cells. However, the agents and mechanism driving this switch have not yet been elucidated. Progranulin (PGRN), a well acknowledged secreted glycoprotein, could promote proliferation and angiogenesis of colorectal cancer (CRC) cells, and high expression of PGRN correlated with patient poor prognosis. Whether PGRN has effects on the function of stromal fibroblasts is unknown. Herein we found that there was a positive correlation between PGRN expression of CRC cells and expressions of smooth muscle actin α (α-SMA) on CAFs in CRC patient tissues. PGRN/α-SMA co-expression was positively correlated with CRC patient poor prognosis. Co-cultured with CRC cells or human recombinant PGRN (rPGRN), the expression of Ki67, fibroblast activation protein (FAP) and α-SMA in fibroblasts were all up-regulated significantly, accompanying with elevated cellular proliferation, migration and contraction. Whilst co-cultured with PGRN-silenced CRC cells, these functions were down-regulated. Studies of the underlying molecular mechanism demonstrated that either tumor necrosis factor receptor 2 (TNFR2)/Akt or the extracellular regulated kinase (ERK) signaling pathway contributed to modulate of Ki67, FAP, and α-SMA expression, and correlated to abilities of proliferation, migration and contraction in fibroblasts. In conclusion, PGRN plays an important role in activation of CRC fibroblasts, which may be taken as a prospective target of CRC therapy.

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Section: Discussioncontrasting

confidence: 47%

Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal cancer

et al. 2017

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“…Matrix fragments may also modulate fibroblast and vascular cell phenotype (44). Endostatin, a 20-kDa fragment of collagen XVIII, exerts potent angiostatic actions (45) and stimulates fibroblast proliferation (46). MMP9-mediated cleavage of collagen IV also generates fragments with angiostatic properties, such as tumstatin (47).…”

Section: Ecm During the Proliferative Phase Of Infarct Healingmentioning

confidence: 99%

The extracellular matrix in myocardial injury, repair, and remodeling

Frangogiannis¹

2017

Journal of Clinical Investigation

400

318

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“…121) In addition, treatment with small interfering (si)RNA against collagen XVIII decreases the survival rate and exacerbates right ventricular remodeling. 121) Endostatin also has biological effects in the heart, such as the inhibition of bradykinin-induced atrial contractions, per-haps through inhibition of the L-type calcium channel 122) and the stimulation of the proliferation and migration of cardiac fibroblasts through activation of the PI3K/Akt signaling pathway. 123) Further study is required to clarify whether endostatin exacerbates or prevents cardiac remodeling.…”

Section: Tumstatinmentioning

confidence: 99%

New Insights into the Role of Basement Membrane-Derived Matricryptins in the Heart

Okada

Imoto

Sugiyama

et al. 2017

Biological & Pharmaceutical Bulletin

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The extracellular matrix (ECM), which contributes to structural homeostasis as well as to the regulation of cellular function, is enzymatically cleaved by proteases, such as matrix metalloproteinases and cathepsins, in the normal and diseased heart. During the past two decades, matricryptins have been defined as fragments of ECM with a biologically active cryptic site, namely the 'matricryptic site,' and their biological activities have been initially identified and clarified, including anti-angiogenic and anti-tumor effects. Thus, matricryptins are expected to be novel anti-tumor drugs, and thus widely investigated. Although there are a smaller number of studies on the expression and function of matricryptins in fields other than cancer research, some matricryptins have been recently clarified to have biological functions beyond an anti-angiogenic effect in heart. This review particularly focuses on the expression and function of basement membrane-derived matricryptins, including arresten, canstatin, tumstatin, endostatin and endorepellin, during cardiac diseases leading to heart failure such as cardiac hypertrophy and myocardial infarction.

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Endostatin stimulates proliferation and migration of adult rat cardiac fibroblasts through PI3K/Akt pathway

Cited by 40 publications

References 31 publications

Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal cancer

Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal cancer

The extracellular matrix in myocardial injury, repair, and remodeling

New Insights into the Role of Basement Membrane-Derived Matricryptins in the Heart

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