3 new research articles for MANF in Osteoarthritis
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Posted On: 03/21/2021 5:16:20 PM
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3 new research articles for MANF in Osteoarthritis, alcoholic pancreatitis, and diabetes.
1) Loss of MANF Causes Childhood-Onset Syndromic Diabetes Due to Increased Endoplasmic Reticulum Stress
Diabetes 2021 Apr; 70(4): 1006-1018.
https://doi.org/10.2337/db20-1174
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)–resident protein that plays a crucial role in attenuating ER stress responses. Although MANF is indispensable for the survival and function of mouse β-cells, its precise role in human β-cell development and function is unknown. In this study, we show that lack of MANF in humans results in diabetes due to increased ER stress, leading to impaired β-cell function. We identified two patients from different families with childhood diabetes and a neurodevelopmental disorder associated with homozygous loss-of-function mutations in the MANF gene. To study the role of MANF in human β-cell development and function, we knocked out the MANF gene in human embryonic stem cells and differentiated them into pancreatic endocrine cells. Loss of MANF induced mild ER stress and impaired insulin-processing capacity of β-cells in vitro. Upon implantation to immunocompromised mice, the MANF knockout grafts presented elevated ER stress and functional failure, particularly in recipients with diabetes. By describing a new form of monogenic neurodevelopmental diabetes syndrome caused by disturbed ER function, we highlight the importance of adequate ER stress regulation for proper human β-cell function and demonstrate the crucial role of MANF in this process.
https://diabetes.diabetesjournals.org/content/70/4/1006
2) MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury
J Hepatobiliary Pancreat Sci
. 2021 Feb 28. doi: 10.1002/jhbp.928. Online ahead of print.
Abstract
Background/purpose: Heavy alcohol drinking is associated with pancreatitis. Pancreatitis is initiated by the damage to the pancreatic acinar cells. The endoplasmic reticulum (ER) stress has been shown to play an important role in alcohol-induced pancreatic damage. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible protein. The aim of the study was to determine whether MANF can ameliorate alcohol-induced ER stress and cellular damages to pancreatic acinar cells.
Methods: Alcohol-induced damage to mouse pancreatic 266-6 acinar cells was determined by MTT and flow cytometry. MANF expression was downregulated by MANF siRNA using the Neon Transfection System. The overexpression of MANF was performed by the infection with the adenoviral vector carrying mouse MANF gene. The expression of ER stress markers was determined by immunoblotting and immunofluorescence.
Results: Alcohol caused ER stress, oxidative stress and induced apoptosis of 266-6 acinar cells. Recombinant human MANF alleviated alcohol-induced ER stress and cell death by inhibiting IRE1-caspase 12-caspase 3 apoptotic pathway. Overexpression of mouse MANF also protected cells against alcohol-induced apoptosis. In contrast, inhibiting MANF by siRNA exacerbated alcohol-induced cellular damage.
Conclusions: MANF was protective against alcohol-induced ER stress and cellular injury in pancreatic acinar cells. The findings suggest a potential therapeutic value of MANF for alcoholic pancreatitis.
3)MANF Produced by MRL Mouse-Derived Mesenchymal Stem Cells Is Pro-regenerative and Protects From Osteoarthritis
Front. Cell Dev. Biol., 02 March 2021 | https://doi.org/10.3389/fcell.2021.579951
Our findings demonstrate that the enhanced regenerative potential of MRL MSC as well as their capacity to tend to reduce OA is attributed, in part, to their capacity to release high amount of MANF.
1) Loss of MANF Causes Childhood-Onset Syndromic Diabetes Due to Increased Endoplasmic Reticulum Stress
Diabetes 2021 Apr; 70(4): 1006-1018.
https://doi.org/10.2337/db20-1174
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)–resident protein that plays a crucial role in attenuating ER stress responses. Although MANF is indispensable for the survival and function of mouse β-cells, its precise role in human β-cell development and function is unknown. In this study, we show that lack of MANF in humans results in diabetes due to increased ER stress, leading to impaired β-cell function. We identified two patients from different families with childhood diabetes and a neurodevelopmental disorder associated with homozygous loss-of-function mutations in the MANF gene. To study the role of MANF in human β-cell development and function, we knocked out the MANF gene in human embryonic stem cells and differentiated them into pancreatic endocrine cells. Loss of MANF induced mild ER stress and impaired insulin-processing capacity of β-cells in vitro. Upon implantation to immunocompromised mice, the MANF knockout grafts presented elevated ER stress and functional failure, particularly in recipients with diabetes. By describing a new form of monogenic neurodevelopmental diabetes syndrome caused by disturbed ER function, we highlight the importance of adequate ER stress regulation for proper human β-cell function and demonstrate the crucial role of MANF in this process.
https://diabetes.diabetesjournals.org/content/70/4/1006
2) MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury
J Hepatobiliary Pancreat Sci
. 2021 Feb 28. doi: 10.1002/jhbp.928. Online ahead of print.
Abstract
Background/purpose: Heavy alcohol drinking is associated with pancreatitis. Pancreatitis is initiated by the damage to the pancreatic acinar cells. The endoplasmic reticulum (ER) stress has been shown to play an important role in alcohol-induced pancreatic damage. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible protein. The aim of the study was to determine whether MANF can ameliorate alcohol-induced ER stress and cellular damages to pancreatic acinar cells.
Methods: Alcohol-induced damage to mouse pancreatic 266-6 acinar cells was determined by MTT and flow cytometry. MANF expression was downregulated by MANF siRNA using the Neon Transfection System. The overexpression of MANF was performed by the infection with the adenoviral vector carrying mouse MANF gene. The expression of ER stress markers was determined by immunoblotting and immunofluorescence.
Results: Alcohol caused ER stress, oxidative stress and induced apoptosis of 266-6 acinar cells. Recombinant human MANF alleviated alcohol-induced ER stress and cell death by inhibiting IRE1-caspase 12-caspase 3 apoptotic pathway. Overexpression of mouse MANF also protected cells against alcohol-induced apoptosis. In contrast, inhibiting MANF by siRNA exacerbated alcohol-induced cellular damage.
Conclusions: MANF was protective against alcohol-induced ER stress and cellular injury in pancreatic acinar cells. The findings suggest a potential therapeutic value of MANF for alcoholic pancreatitis.
3)MANF Produced by MRL Mouse-Derived Mesenchymal Stem Cells Is Pro-regenerative and Protects From Osteoarthritis
Front. Cell Dev. Biol., 02 March 2021 | https://doi.org/10.3389/fcell.2021.579951
Our findings demonstrate that the enhanced regenerative potential of MRL MSC as well as their capacity to tend to reduce OA is attributed, in part, to their capacity to release high amount of MANF.
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