scholarly journals CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Zeng ◽  
Zhenzhen Zhang ◽  
Qing Liao ◽  
Qijin Lu ◽  
Jiemei Liu ◽  
...  
Keyword(s):  
Drug Development ◽  
Matrix Metalloproteinase ◽  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Beclin 1 ◽  
Matrix Metalloproteinase 13 ◽  
Autophagy Induction ◽  
Ghrelin Gene ◽  
A Disintegrin And Metalloproteinase ◽  
And Cartilage

This study aimed to investigate the potential roles of circRNAs in regulating osteoarthritis (OA)-related ghrelin synthesis, autophagy induction, and the relevant molecular mechanisms. Results showed that Col2a1, Acan, ghrelin, and autophagy-related markers expression were downregulated, while matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) expressions increased in both IL-1β-induced rat chondrocytes and cartilage tissues of OA rats. A total of 130 circRNAs and 731 mRNAs were differentially expressed in IL-1β-induced rat chondrocytes. Among them, we found that circPan3 expression was significantly decreased in both cellular and animal OA models. CircPan3 directly targeted miR-667-5p. CircPan3 overexpression promoted Col2a1, Acan, ghrelin, beclin 1, and LC3-II expression but reduced MMP13 and ADAMTS5 expression in rat chondrocytes, whereas overexpression of miR-667-5p exhibited opposite effects on the above markers. Furthermore, we found that miR-667-5p bound directly to the 3′-UTR sequence of ghrelin gene. Moreover, the circPan3-induced alterations in chondrocytes were antagonized by miR-667-5p overexpression. Taken together, our findings demonstrate that circPan3 promotes ghrelin synthesis and chondrocyte autophagy via targeting miR-667-5p, protecting against OA injury. This study provided experimental evidence that circPan3/miR-667-5p/ghrelin axis might serve as targets of drug development for the treatment of OA.

scholarly journals Matrix Metalloproteinase 13 Activity is Required for Normal and Hypoxia-Induced Precocious Hatching in Zebrafish Embryos

2020 ◽  
Vol 8 (1) ◽  
pp. 3
Author(s):  
Christopher D. Small ◽  
Megan el-Khoury ◽  
Ghislain Deslongchamps ◽  
Tillmann J. Benfey ◽  
Bryan D. Crawford
Keyword(s):  
Matrix Metalloproteinase ◽  
Environmental Conditions ◽  
Molecular Mechanisms ◽  
Zebrafish Embryos ◽  
Clear Understanding ◽  
Hatching Enzyme ◽  
Pharmacological Inhibition ◽  
Matrix Metalloproteinase 13 ◽  
Hatching Gland

Hypoxia induces precocious hatching in zebrafish, but we do not have a clear understanding of the molecular mechanisms regulating the activation of the hatching enzyme or how these mechanisms trigger precocious hatching under unfavorable environmental conditions. Using immunohistochemistry, pharmacological inhibition of matrix metalloproteinase 13 (Mmp13), and in vivo zymography, we show that Mmp13a is present in the hatching gland just as embryos become hatching competent and that Mmp13a activity is required for both normal hatching and hypoxia-induced precocious hatching. We conclude that Mmp13a likely functions in activating the hatching enzyme zymogen and that Mmp13a activity is necessary but not sufficient for hatching in zebrafish. This study highlights the broad nature of MMP function in development and provides a non-mammalian example of extra-embryonic processes mediated by MMP activity.

scholarly journals Reactive Oxygen Species-Mediated c-Jun NH2-Terminal Kinase Activation Contributes to Hepatitis B Virus X Protein-Induced Autophagy via Regulation of the Beclin-1/Bcl-2 Interaction

2017 ◽  
Vol 91 (15) ◽  
Author(s):  
Linmao Zhong ◽  
Wangqin Shu ◽  
Wangbin Dai ◽  
Bo Gao ◽  
Sidong Xiong
Keyword(s):  
Molecular Mechanisms ◽  
Beclin 1 ◽  
Biological Processes ◽  
Class Iii ◽  
Autophagosome Formation ◽  
Jnk Signaling ◽  
Hbv Replication ◽  
Autophagy Induction ◽  
B Virus ◽  
Jnk Activation

ABSTRACT Autophagy is closely associated with the regulation of hepatitis B virus (HBV) replication. HBV X protein (HBx), a multifunctional regulator in HBV-associated biological processes, has been demonstrated to be crucial for autophagy induction by HBV. However, the molecular mechanisms of autophagy induction by HBx, especially the signaling pathways involved, remain elusive. In the present investigation, we demonstrated that HBx induced autophagosome formation independently of the class I phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway. In contrast, the class III PI3K(VPS34)/beclin-1 pathway was revealed to be critical for HBx-induced autophagosome formation. Further study showed that HBx did not affect the level of VPS34 and beclin-1 expression but inhibited beclin-1/Bcl-2 association, and c-Jun NH2-terminal kinase (JNK) signaling was found to be important for this process. Moreover, it was found that HBx treatment led to the generation of reactive oxygen species (ROS), and inhibition of ROS activity abrogated both JNK activation and autophagosome formation. Of importance, ROS-JNK signaling was also revealed to play an important role in HBV-induced autophagosome formation and subsequent HBV replication. These data may provide deeper insight into the mechanisms of autophagy induction by HBx and help in the design of new therapeutic strategies against HBV infection. IMPORTANCE HBx plays a key role in diverse HBV-associated biological processes, including autophagy induction. However, the molecular mechanisms of autophagy induction by HBx, especially the signaling pathways involved, remain elusive. In the present investigation, we found that HBx induced autophagy independently of the class I PI3K/AKT/mTOR signaling pathway, while the class III PI3K(VPS34)/beclin-1 pathway was revealed to be crucial for this process. Further data showed that ROS-JNK activation by HBx resulted in the release of beclin-1 from its association with Bcl-2 to form a complex with VPS34, thus enhancing autophagosome formation. Of importance, ROS-JNK signaling was also demonstrated to be critical for HBV replication via regulation of autophagy induction. These data help to elucidate the molecular mechanisms of autophagy induction by HBx/HBV and might be useful for designing novel therapeutic approaches to HBV infection.

scholarly journals Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis

2021 ◽  
Vol 22 (4) ◽  
pp. 1742
Author(s):  
Qichan Hu ◽  
Melanie Ecker
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Type Ii ◽  
Inhibitor Development ◽  
Matrix Metalloproteinase 13 ◽  
Promising Target

Osteoarthritis (OA) is a common degenerative disease characterized by the destruction of articular cartilage and chronic inflammation of surrounding tissues. Matrix metalloproteinase-13 (MMP-13) is the primary MMP involved in cartilage degradation through its particular ability to cleave type II collagen. Hence, it is an attractive target for the treatment of OA. However, the detailed molecular mechanisms of OA initiation and progression remain elusive, and, currently, there are no interventions available to restore degraded cartilage. This review fully illustrates the involvement of MMP-13 in the initiation and progression of OA through the regulation of MMP-13 activity at the molecular and epigenetic levels, as well as the strategies that have been employed against MMP-13. The aim of this review is to identify MMP-13 as an attractive target for inhibitor development in the treatment of OA.

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