MTMR14 protects against hepatic ischemia-reperfusion injury through interacting with AKT signaling in vivo and in vitro

Li, Shufang; Zhang, Meng; Zhang, Bei

doi:10.1016/j.biopha.2020.110455

Cited by 4 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zhang et al reported that the prevention of cardiac hypertrophy by MTMR14 involves the elevation of Akt pathway components [42]. In addition, Li et al showed that MTMR14 plays a protective role in hepatic ischemia-reperfusion injury by interacting with the Akt signaling pathway [43]. The Akt signaling pathway is also a key component in the regulation of inflammation and emphysema in COPD [44,45].…”

Section: Discussionmentioning

confidence: 99%

MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema

Chen

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients’ lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro. Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD.

show abstract

Section: Discussionmentioning

confidence: 99%

MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema

Chen

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…The most well-known and distinguished effect of MTMRs is the ability to dephosphorylate phosphatidylinositol 3-monophosphate (PI(3)P) and phosphatidylinositol ( 3 , 5 ) bis-phosphate (PI(3,5)P2), indicating MTMRs are involved in cellular membrane transport and endocytosis ( 5 ). MTMRs are widely expressed in different kind of tissue and organs, including the neural system, heart, liver, testicle and gastrointestinal tract ( 6 – 8 ). MTMRs also exert multiple physiological roles such as modulating cell proliferation, differentiation, necrosis and migration ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases

Wang,

Guo,

Wang

et al. 2024

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Belonging to a lipid phosphatase family containing 16 members, myotubularin-related proteins (MTMRs) are widely expressed in a variety of tissues and organs. MTMRs preferentially hydrolyzes phosphatidylinositol 3-monophosphate and phosphatidylinositol (3,5) bis-phosphate to generate phosphatidylinositol and phosphatidylinositol 5-monophosphate, respectively. These phosphoinositides (PIPs) promote membrane degradation during autophagosome-lysosomal fusion and are also involved in various regulatory signal transduction. Based on the ability of modulating the levels of these PIPs, MTMRs exert physiological functions such as vesicle trafficking, cell proliferation, differentiation, necrosis, cytoskeleton, and cell migration. It has recently been found that MTMRs are also involved in the occurrence and development of several cardiovascular diseases, including cardiomyocyte hypertrophy, proliferation of vascular smooth muscle cell, LQT1, aortic aneurysm, etc. This review summarizes the functions of MTMRs and highlights their pathophysiological roles in cardiovascular diseases.

show abstract

“… 10 In addition, MTMR14 may play a biological role by regulating the star molecule AKT. 11 , 12 However, the function of MTMR14 in VSMC is less studied.…”

mentioning

confidence: 99%

Myotubularin‐Related Protein14 Prevents Neointima Formation and Vascular Smooth Muscle Cell Proliferation by Inhibiting Polo‐Like Kinase1

Kong

Liang

et al. 2022

JAHA

View full text Add to dashboard Cite

Background Restenosis is one of the main bottlenecks in restricting the further development of cardiovascular interventional therapy. New signaling molecules involved in the progress have continuously been discovered; however, the specific molecular mechanisms remain unclear. MTMR14 (myotubularin‐related protein 14) is a novel phosphoinositide phosphatase that has a variety of biological functions and is involved in diverse biological processes. However, the role of MTMR14 in vascular biology remains unclear. Herein, we addressed the role of MTMR14 in neointima formation and vascular smooth muscle cell (VSMC) proliferation after vessel injury. Methods and Results Vessel injury models were established using SMC‐specific conditional MTMR14‐knockout and ‐transgenic mice. Neointima formation was assessed by histopathological methods, and VSMC proliferation and migration were assessed using fluorescence ubiquitination‐based cell cycle indicator, transwell, and scratch wound assay. Neointima formation and the expression of MTMR14 was increased after injury. MTMR14 deficiency accelerated neointima formation and promoted VSMC proliferation after injury, whereas MTMR14 overexpression remarkably attenuated this process. Mechanistically, we demonstrated that MTMR14 suppressed the activation of PLK1 (polo‐like kinase 1) by interacting with it, which further leads to the inhibition of the activation of MEK/ERK/AKT (mitogen‐activated protein kinase kinase/extracellular‐signal‐regulated kinase/protein kinase B), thereby inhibiting the proliferation of VSMC from the medial to the intima and thus preventing neointima formation. Conclusions MTMR14 prevents neointima formation and VSMC proliferation by inhibiting PLK1. Our findings reveal that MTMR14 serves as an inhibitor of VSMC proliferation and establish a link between MTMR14 and PLK1 in regulating VSMC proliferation. MTMR14 may become a novel potential therapeutic target in the treatment of restenosis.

show abstract

MTMR14 protects against hepatic ischemia-reperfusion injury through interacting with AKT signaling in vivo and in vitro

Cited by 4 publications

References 39 publications

MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema

MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema

Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases

Myotubularin‐Related Protein14 Prevents Neointima Formation and Vascular Smooth Muscle Cell Proliferation by Inhibiting Polo‐Like Kinase1

Contact Info

Product

Resources

About