Emilin2 fosters vascular stability by promoting pericyte recruitment
In this study, we discovered that the extracellular matrix glycoprotein Elastin Microfibril Interfacer 2 (Emilin2) plays a prominent role in pericyte physiology. This work was originally prompted by the observations that tumor-associated vessels from Emilin2-/- mice display less pericyte coverage, impaired vascular perfusion, and reduced drug efficacy, suggesting that Emilin2 could promote vessel maturation and stabilization affecting pericyte recruitment. We found that Emilin2 affects different mechanisms engaged in pericyte recruitment and vascular stabilization. First, human primary endothelial cells challenged with rec...
Source: Matrix Biology - August 14, 2023 Category: Molecular Biology Authors: Albina Fejza Lucrezia Camicia Greta Carobolante Evelina Poletto Alice Paulitti Giorgia Schinello Emanuele Di Siena Renato Cannizzaro Renato V Iozzo Gustavo Baldassarre Eva Andreuzzi Paola Spessotto Maurizio Mongiat Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation
In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with gluta...
Source: Matrix Biology - August 4, 2023 Category: Molecular Biology Authors: Xinru Xue Xi Zeng Xiaoqian Wu Kexin Mu Yue Dai Zhifeng Wei Source Type: research
The extracellular matrix - immune microenvironment crosstalk in cancer therapy: challenges and opportunities
Matrix Biol. 2023 Jul 29:S0945-053X(23)00081-1. doi: 10.1016/j.matbio.2023.07.003. Online ahead of print.ABSTRACTTargeting the tumour immune microenvironment (TIME) by cancer immunotherapy has led to improved patient outcomes. However, response to these treatments is heterogeneous and cancer-type dependent. The therapeutic activity of classical cancer therapies such as chemotherapy, radiotherapy, and surgical oncology is modulated by alterations of the TIME. A major regulator of immune cell function and resistance to both immune and classical therapies is the extracellular matrix (ECM). Concurrently, cancer therapies resha...
Source: Matrix Biology - July 31, 2023 Category: Molecular Biology Authors: Lara Closset Okan Gultekin Sahar Salehi Dhifaf Sarhan Kaisa Lehti Jordi Gonzalez-Molina Source Type: research
The extracellular matrix - immune microenvironment crosstalk in cancer therapy: challenges and opportunities
Matrix Biol. 2023 Jul 29:S0945-053X(23)00081-1. doi: 10.1016/j.matbio.2023.07.003. Online ahead of print.ABSTRACTTargeting the tumour immune microenvironment (TIME) by cancer immunotherapy has led to improved patient outcomes. However, response to these treatments is heterogeneous and cancer-type dependent. The therapeutic activity of classical cancer therapies such as chemotherapy, radiotherapy, and surgical oncology is modulated by alterations of the TIME. A major regulator of immune cell function and resistance to both immune and classical therapies is the extracellular matrix (ECM). Concurrently, cancer therapies resha...
Source: Matrix Biology - July 31, 2023 Category: Molecular Biology Authors: Lara Closset Okan Gultekin Sahar Salehi Dhifaf Sarhan Kaisa Lehti Jordi Gonzalez-Molina Source Type: research
The extracellular matrix - immune microenvironment crosstalk in cancer therapy: challenges and opportunities
Matrix Biol. 2023 Jul 29:S0945-053X(23)00081-1. doi: 10.1016/j.matbio.2023.07.003. Online ahead of print.ABSTRACTTargeting the tumour immune microenvironment (TIME) by cancer immunotherapy has led to improved patient outcomes. However, response to these treatments is heterogeneous and cancer-type dependent. The therapeutic activity of classical cancer therapies such as chemotherapy, radiotherapy, and surgical oncology is modulated by alterations of the TIME. A major regulator of immune cell function and resistance to both immune and classical therapies is the extracellular matrix (ECM). Concurrently, cancer therapies resha...
Source: Matrix Biology - July 31, 2023 Category: Molecular Biology Authors: Lara Closset Okan Gultekin Sahar Salehi Dhifaf Sarhan Kaisa Lehti Jordi Gonzalez-Molina Source Type: research
The extracellular matrix - immune microenvironment crosstalk in cancer therapy: challenges and opportunities
Matrix Biol. 2023 Jul 29:S0945-053X(23)00081-1. doi: 10.1016/j.matbio.2023.07.003. Online ahead of print.ABSTRACTTargeting the tumour immune microenvironment (TIME) by cancer immunotherapy has led to improved patient outcomes. However, response to these treatments is heterogeneous and cancer-type dependent. The therapeutic activity of classical cancer therapies such as chemotherapy, radiotherapy, and surgical oncology is modulated by alterations of the TIME. A major regulator of immune cell function and resistance to both immune and classical therapies is the extracellular matrix (ECM). Concurrently, cancer therapies resha...
Source: Matrix Biology - July 31, 2023 Category: Molecular Biology Authors: Lara Closset Okan Gultekin Sahar Salehi Dhifaf Sarhan Kaisa Lehti Jordi Gonzalez-Molina Source Type: research
The clock transcription factor BMAL1 is a key regulator of extracellular matrix homeostasis and cell fate in the intervertebral disc
Matrix Biol. 2023 Jul 24:S0945-053X(23)00080-X. doi: 10.1016/j.matbio.2023.07.002. Online ahead of print.ABSTRACTThe circadian clock in mammals temporally coordinates physiological and behavioural processes to anticipate daily rhythmic changes in their environment. Chronic disruption to circadian rhythms (e.g., through ageing or shift work) is thought to contribute to a multitude of diseases, including degeneration of the musculoskeletal system. The intervertebral disc (IVD) in the spine contains circadian clocks which control ∼6% of the transcriptome in a rhythmic manner, including key genes involved in extracellular ma...
Source: Matrix Biology - July 26, 2023 Category: Molecular Biology Authors: Michal Dudek Honor Morris Natalie Rogers Dharshika Rj Pathiranage Sujitha Saba Raj Danny Chan Karl E Kadler Judith Hoyland Qing-Jun Meng Source Type: research
The clock transcription factor BMAL1 is a key regulator of extracellular matrix homeostasis and cell fate in the intervertebral disc
Matrix Biol. 2023 Jul 24:S0945-053X(23)00080-X. doi: 10.1016/j.matbio.2023.07.002. Online ahead of print.ABSTRACTThe circadian clock in mammals temporally coordinates physiological and behavioural processes to anticipate daily rhythmic changes in their environment. Chronic disruption to circadian rhythms (e.g., through ageing or shift work) is thought to contribute to a multitude of diseases, including degeneration of the musculoskeletal system. The intervertebral disc (IVD) in the spine contains circadian clocks which control ∼6% of the transcriptome in a rhythmic manner, including key genes involved in extracellular ma...
Source: Matrix Biology - July 26, 2023 Category: Molecular Biology Authors: Michal Dudek Honor Morris Natalie Rogers Dharshika Rj Pathiranage Sujitha Saba Raj Danny Chan Karl E Kadler Judith Hoyland Qing-Jun Meng Source Type: research
