The Experts below are selected from a list of 161353953 Experts worldwide ranked by ideXlab platform
Brian C. Mansfield - One of the best experts on this subject based on the ideXlab platform.
-
molecular biology and gene therapy for glycogen storage disease type ib
Journal of Inherited Metabolic Disease, 2018Co-Authors: Janice Y. Chou, Jun-ho Cho, Goo-young Kim, Brian C. MansfieldAbstract:Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose-6-phosphate (G6P) transporter (G6PT or SLC37A4). The primary function of G6PT is to translocate G6P from the cytoplasm into the lumen of the endoplasmic reticulum (ER). Inside the ER, G6P is hydrolyzed to glucose and phosphate by either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α) or the ubiquitously expressed G6Pase-β. A deficiency in G6Pase-α causes GSD type Ia (GSD-Ia) and a deficiency in G6Pase-β causes GSD-I-related syndrome (GSD-Irs). In gluconeogenic organs, functional coupling of G6PT and G6Pase-α is required to maintain interprandial blood glucose homeostasis. In myeloid tissues, functional coupling of G6PT and G6Pase-β is required to maintain neutrophil homeostasis. Accordingly, GSD-Ib is a metabolic and immune disorder, manifesting impaired glucose homeostasis, neutropenia, and neutrophil dysfunction. A G6pt knockout mouse model is being exploited to delineate the pathophysiology of GSD-Ib and develop new clinical treatment options, including gene therapy. The safety and efficacy of several G6PT-expressing recombinant adeno-associated virus pseudotype 2/8 vectors have been examined in murine GSD-Ib. The results demonstrate that the liver-directed gene transfer and expression safely corrects metabolic abnormalities and prevents hepatocellular adenoma (HCA) development. However, a second vector system may be required to correct myeloid and renal dysfunction in GSD-Ib. These findings are paving the way to a safe and efficacious gene therapy for entering clinical trials.
-
The SLC37 family of sugar-phosphate/phosphate exchangers.
Current topics in membranes, 2014Co-Authors: Janice Y. Chou, Brian C. MansfieldAbstract:The SLC37 family members are endoplasmic reticulum (ER)-associated sugar-phosphate/phosphate (Pi) exchangers. Three of the four members, SLC37A1, SLC37A2, and SLC37A4, function as Pi-linked glucose-6-phosphate (G6P) antiporters catalyzing G6P:Pi and Pi:Pi exchanges. The activity of SLC37A3 is unknown. SLC37A4, better known as the G6P transporter (G6PT), has been extensively characterized, functionally and structurally, and is the best characterized family member. G6PT contains 10 transmembrane helices with both N and C termini facing the cytoplasm. The primary in vivo function of the G6PT protein is to translocate G6P from the cytoplasm into the ER lumen where it couples with either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α or G6PC) or the ubiquitously expressed G6Pase-β (or G6PC3) to hydrolyze G6P to glucose and Pi. The G6PT/G6Pase-α complex maintains interprandial glucose homeostasis, and the G6PT/G6Pase-β complex maintains neutro-phil energy homeostasis and functionality. G6PT is highly selective for G6P and is competitively inhibited by cholorogenic acid and its derivatives. Neither SLC37A1 nor SLC37A2 can couple functionally with G6Pase-α or G6Pase-β, and the antiporter activities of SLC37A1 or SLC37A2 are not inhibited by cholorogenic acid. Deficiencies in G6PT cause glycogen storage disease type Ib (GSD-Ib), a metabolic and immune disorder. To date, 91 separate SLC37A4 mutations, including 39 missense mutations, have been identified in GSD-Ib patients. Characterization of missense mutations has yielded valuable information on functionally important residues in the G6PT protein. The biological roles of the other SLC37 proteins remain to be determined and deficiencies have not yet been correlated to diseases.
-
The SLC37 family of phosphate-linked sugar phosphate antiporters.
Molecular aspects of medicine, 2013Co-Authors: Janice Y. Chou, Hyun Sik Jun, Brian C. MansfieldAbstract:The SLC37 family consists of four sugar-phosphate exchangers, A1, A2, A3, and A4, which are anchored in the endoplasmic reticulum (ER) membrane. The best characterized family member is SLC37A4, better known as the glucose-6-phosphate (G6P) transporter (G6PT). SLC37A1, SLC37A2, and G6PT function as phosphate (Pi)-linked G6P antiporters catalyzing G6P:Pi and Pi:Pi exchanges. The activity of SLC37A3 is unknown. G6PT translocates G6P from the cytoplasm into the lumen of the ER where it couples with either glucose-6-phosphatase-α (G6Pase-α) or G6Pase-β to hydrolyze intraluminal G6P to glucose and Pi. The functional coupling of G6PT with G6Pase-α maintains interprandial glucose homeostasis and the functional coupling of G6PT with G6Pase-β maintains neutrophil energy homeostasis and functionality. A deficiency in G6PT causes glycogen storage disease type Ib, an autosomal recessive disorder characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction. Neither SLC37A1 nor SLC37A2 can functionally couple with G6Pase-α or G6Pase-β, and there are no known disease associations for them or SLC37A3. Since only G6PT matches the characteristics of the physiological ER G6P transporter involved in blood glucose homeostasis and neutrophil energy metabolism, the biological roles for the other SLC37 proteins remain to be determined.
-
SLC37A1 and SLC37A2 Are Phosphate-Linked, Glucose-6-Phosphate Antiporters
PloS one, 2011Co-Authors: Chi-jiunn Pan, Brian C. Mansfield, Hyun Sik Jun, Shih Yin Chen, Su Ru Lin, Janice Y. ChouAbstract:Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (Pi). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a Pi-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis.
Janice Y. Chou - One of the best experts on this subject based on the ideXlab platform.
-
molecular biology and gene therapy for glycogen storage disease type ib
Journal of Inherited Metabolic Disease, 2018Co-Authors: Janice Y. Chou, Jun-ho Cho, Goo-young Kim, Brian C. MansfieldAbstract:Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose-6-phosphate (G6P) transporter (G6PT or SLC37A4). The primary function of G6PT is to translocate G6P from the cytoplasm into the lumen of the endoplasmic reticulum (ER). Inside the ER, G6P is hydrolyzed to glucose and phosphate by either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α) or the ubiquitously expressed G6Pase-β. A deficiency in G6Pase-α causes GSD type Ia (GSD-Ia) and a deficiency in G6Pase-β causes GSD-I-related syndrome (GSD-Irs). In gluconeogenic organs, functional coupling of G6PT and G6Pase-α is required to maintain interprandial blood glucose homeostasis. In myeloid tissues, functional coupling of G6PT and G6Pase-β is required to maintain neutrophil homeostasis. Accordingly, GSD-Ib is a metabolic and immune disorder, manifesting impaired glucose homeostasis, neutropenia, and neutrophil dysfunction. A G6pt knockout mouse model is being exploited to delineate the pathophysiology of GSD-Ib and develop new clinical treatment options, including gene therapy. The safety and efficacy of several G6PT-expressing recombinant adeno-associated virus pseudotype 2/8 vectors have been examined in murine GSD-Ib. The results demonstrate that the liver-directed gene transfer and expression safely corrects metabolic abnormalities and prevents hepatocellular adenoma (HCA) development. However, a second vector system may be required to correct myeloid and renal dysfunction in GSD-Ib. These findings are paving the way to a safe and efficacious gene therapy for entering clinical trials.
-
The SLC37 family of sugar-phosphate/phosphate exchangers.
Current topics in membranes, 2014Co-Authors: Janice Y. Chou, Brian C. MansfieldAbstract:The SLC37 family members are endoplasmic reticulum (ER)-associated sugar-phosphate/phosphate (Pi) exchangers. Three of the four members, SLC37A1, SLC37A2, and SLC37A4, function as Pi-linked glucose-6-phosphate (G6P) antiporters catalyzing G6P:Pi and Pi:Pi exchanges. The activity of SLC37A3 is unknown. SLC37A4, better known as the G6P transporter (G6PT), has been extensively characterized, functionally and structurally, and is the best characterized family member. G6PT contains 10 transmembrane helices with both N and C termini facing the cytoplasm. The primary in vivo function of the G6PT protein is to translocate G6P from the cytoplasm into the ER lumen where it couples with either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α or G6PC) or the ubiquitously expressed G6Pase-β (or G6PC3) to hydrolyze G6P to glucose and Pi. The G6PT/G6Pase-α complex maintains interprandial glucose homeostasis, and the G6PT/G6Pase-β complex maintains neutro-phil energy homeostasis and functionality. G6PT is highly selective for G6P and is competitively inhibited by cholorogenic acid and its derivatives. Neither SLC37A1 nor SLC37A2 can couple functionally with G6Pase-α or G6Pase-β, and the antiporter activities of SLC37A1 or SLC37A2 are not inhibited by cholorogenic acid. Deficiencies in G6PT cause glycogen storage disease type Ib (GSD-Ib), a metabolic and immune disorder. To date, 91 separate SLC37A4 mutations, including 39 missense mutations, have been identified in GSD-Ib patients. Characterization of missense mutations has yielded valuable information on functionally important residues in the G6PT protein. The biological roles of the other SLC37 proteins remain to be determined and deficiencies have not yet been correlated to diseases.
-
The SLC37 family of phosphate-linked sugar phosphate antiporters.
Molecular aspects of medicine, 2013Co-Authors: Janice Y. Chou, Hyun Sik Jun, Brian C. MansfieldAbstract:The SLC37 family consists of four sugar-phosphate exchangers, A1, A2, A3, and A4, which are anchored in the endoplasmic reticulum (ER) membrane. The best characterized family member is SLC37A4, better known as the glucose-6-phosphate (G6P) transporter (G6PT). SLC37A1, SLC37A2, and G6PT function as phosphate (Pi)-linked G6P antiporters catalyzing G6P:Pi and Pi:Pi exchanges. The activity of SLC37A3 is unknown. G6PT translocates G6P from the cytoplasm into the lumen of the ER where it couples with either glucose-6-phosphatase-α (G6Pase-α) or G6Pase-β to hydrolyze intraluminal G6P to glucose and Pi. The functional coupling of G6PT with G6Pase-α maintains interprandial glucose homeostasis and the functional coupling of G6PT with G6Pase-β maintains neutrophil energy homeostasis and functionality. A deficiency in G6PT causes glycogen storage disease type Ib, an autosomal recessive disorder characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction. Neither SLC37A1 nor SLC37A2 can functionally couple with G6Pase-α or G6Pase-β, and there are no known disease associations for them or SLC37A3. Since only G6PT matches the characteristics of the physiological ER G6P transporter involved in blood glucose homeostasis and neutrophil energy metabolism, the biological roles for the other SLC37 proteins remain to be determined.
-
SLC37A1 and SLC37A2 Are Phosphate-Linked, Glucose-6-Phosphate Antiporters
PloS one, 2011Co-Authors: Chi-jiunn Pan, Brian C. Mansfield, Hyun Sik Jun, Shih Yin Chen, Su Ru Lin, Janice Y. ChouAbstract:Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (Pi). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a Pi-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis.
Pietro Strisciuglio - One of the best experts on this subject based on the ideXlab platform.
-
Insulin-resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria?
Journal of Inherited Metabolic Disease, 2018Co-Authors: Alessandro Rossi, Giancarlo Parenti, Margherita Ruoppolo, Pietro Formisano, Guglielmo Villani, Lucia Albano, Giovanna Gallo, Daniela Crisci, Augusta Moccia, Pietro StrisciuglioAbstract:Background Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Mitochondrial dysfunction can demonstrate abnormalities in plama acylcarnitines (ACs) and urine organic acids (UOA). The aim of the study was to investigate the presence of mitochondrial impairment in GSDI patients and its possible connection with IR. Methods Fourteen GSDIa, seven GSDIb patients, 28 and 14 age and sex-matched controls, were enrolled. Plasma ACs, UOA, and surrogate markers of IR (HOMA-IR, QUICKI, ISI, VAI) were measured. Results GSDIa patients showed higher short-chain ACs and long-chain ACs levels and increased urinary excretion of lactate, pyruvate, 2-ketoglutarate, 3-methylglutaconate, adipate, suberate, aconitate, ethylmalonate, fumarate, malate, sebacate, 4-octenedioate, 3OH-suberate, and 3-methylglutarate than controls (p
-
Insulin‐resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria?
Journal of inherited metabolic disease, 2018Co-Authors: Alessandro Rossi, Giancarlo Parenti, Margherita Ruoppolo, Pietro Formisano, Lucia Albano, Giovanna Gallo, Daniela Crisci, Augusta Moccia, Guglielmo R. D. Villani, Pietro StrisciuglioAbstract:Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Mitochondrial dysfunction can demonstrate abnormalities in plama acylcarnitines (ACs) and urine organic acids (UOA). The aim of the study was to investigate the presence of mitochondrial impairment in GSDI patients and its possible connection with IR. Fourteen GSDIa, seven GSDIb patients, 28 and 14 age and sex-matched controls, were enrolled. Plasma ACs, UOA, and surrogate markers of IR (HOMA-IR, QUICKI, ISI, VAI) were measured. GSDIa patients showed higher short-chain ACs and long-chain ACs levels and increased urinary excretion of lactate, pyruvate, 2-ketoglutarate, 3-methylglutaconate, adipate, suberate, aconitate, ethylmalonate, fumarate, malate, sebacate, 4-octenedioate, 3OH-suberate, and 3-methylglutarate than controls (p
Alessandro Rossi - One of the best experts on this subject based on the ideXlab platform.
-
Insulin-resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria?
Journal of Inherited Metabolic Disease, 2018Co-Authors: Alessandro Rossi, Giancarlo Parenti, Margherita Ruoppolo, Pietro Formisano, Guglielmo Villani, Lucia Albano, Giovanna Gallo, Daniela Crisci, Augusta Moccia, Pietro StrisciuglioAbstract:Background Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Mitochondrial dysfunction can demonstrate abnormalities in plama acylcarnitines (ACs) and urine organic acids (UOA). The aim of the study was to investigate the presence of mitochondrial impairment in GSDI patients and its possible connection with IR. Methods Fourteen GSDIa, seven GSDIb patients, 28 and 14 age and sex-matched controls, were enrolled. Plasma ACs, UOA, and surrogate markers of IR (HOMA-IR, QUICKI, ISI, VAI) were measured. Results GSDIa patients showed higher short-chain ACs and long-chain ACs levels and increased urinary excretion of lactate, pyruvate, 2-ketoglutarate, 3-methylglutaconate, adipate, suberate, aconitate, ethylmalonate, fumarate, malate, sebacate, 4-octenedioate, 3OH-suberate, and 3-methylglutarate than controls (p
-
Insulin‐resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria?
Journal of inherited metabolic disease, 2018Co-Authors: Alessandro Rossi, Giancarlo Parenti, Margherita Ruoppolo, Pietro Formisano, Lucia Albano, Giovanna Gallo, Daniela Crisci, Augusta Moccia, Guglielmo R. D. Villani, Pietro StrisciuglioAbstract:Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Mitochondrial dysfunction can demonstrate abnormalities in plama acylcarnitines (ACs) and urine organic acids (UOA). The aim of the study was to investigate the presence of mitochondrial impairment in GSDI patients and its possible connection with IR. Fourteen GSDIa, seven GSDIb patients, 28 and 14 age and sex-matched controls, were enrolled. Plasma ACs, UOA, and surrogate markers of IR (HOMA-IR, QUICKI, ISI, VAI) were measured. GSDIa patients showed higher short-chain ACs and long-chain ACs levels and increased urinary excretion of lactate, pyruvate, 2-ketoglutarate, 3-methylglutaconate, adipate, suberate, aconitate, ethylmalonate, fumarate, malate, sebacate, 4-octenedioate, 3OH-suberate, and 3-methylglutarate than controls (p
-
Involvement of endocrine system in a patient affected by Glycogen storage disease 1b: speculation on the role of autoimmunity
Italian Journal of Pediatrics, 2014Co-Authors: Daniela Melis, Generoso Andria, Roberto Della Casa, Francesca Balivo, Giorgia Minopoli, Alessandro Rossi, Mariacarolina Salerno, Giancarlo ParentiAbstract:Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.
Ute Spiekerkoetter - One of the best experts on this subject based on the ideXlab platform.
-
Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib
Orphanet Journal of Rare Diseases, 2020Co-Authors: Sarah C. Grünert, Saskia B. Wortmann, Roland Elling, Bärbel Maag, Terry G. J. Derks, Luciana Hannibal, Anke Schumann, Stefanie Rosenbaum-fabian, Ute SpiekerkoetterAbstract:Background Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4 . Besides a severe form of fasting intolerance, the disorder is usually associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease, oral, urogenital and perianal lesions as well as impaired wound healing. Recently, SGLT2 inhibitors such as empagliflozin that reduce the plasma levels of 1,5-anhydroglucitol have been described as a new treatment option for the neutropenia and neutrophil dysfunction in patients with GSD Ib. Results We report on a 35-year-old female patient with GSD Ib who had been treated with G-CSF for neutropenia since the age of 9. She had a large chronic abdominal wound as a consequence of recurrent operations due to complications of her inflammatory bowel disease. Treatment with 20 mg empagliflozin per day resulted in normalisation of the neutrophil count and neutrophil function even after termination of G-CSF. The chronic abdominal wound that had been unchanged for 2 years before the start of empagliflozin nearly closed within 12 weeks. No side effects of empagliflozin were observed. Conclusion SGLT2 inhibitors are a new and probably safe treatment option for GSD Ib-associated neutropenia and neutrophil dysfunction. We hypothesize that restoration of neutrophil function and normalisation of neutrophil apoptosis leads to improvement of wound healing and ameliorates symptoms of inflammatory bowel disease.
-
Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib.
Orphanet journal of rare diseases, 2020Co-Authors: Sarah C. Grünert, Saskia B. Wortmann, Roland Elling, Bärbel Maag, Terry G. J. Derks, Luciana Hannibal, Anke Schumann, Stefanie Rosenbaum-fabian, Ute SpiekerkoetterAbstract:Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. Besides a severe form of fasting intolerance, the disorder is usually associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease, oral, urogenital and perianal lesions as well as impaired wound healing. Recently, SGLT2 inhibitors such as empagliflozin that reduce the plasma levels of 1,5-anhydroglucitol have been described as a new treatment option for the neutropenia and neutrophil dysfunction in patients with GSD Ib. We report on a 35-year-old female patient with GSD Ib who had been treated with G-CSF for neutropenia since the age of 9. She had a large chronic abdominal wound as a consequence of recurrent operations due to complications of her inflammatory bowel disease. Treatment with 20 mg empagliflozin per day resulted in normalisation of the neutrophil count and neutrophil function even after termination of G-CSF. The chronic abdominal wound that had been unchanged for 2 years before the start of empagliflozin nearly closed within 12 weeks. No side effects of empagliflozin were observed. SGLT2 inhibitors are a new and probably safe treatment option for GSD Ib-associated neutropenia and neutrophil dysfunction. We hypothesize that restoration of neutrophil function and normalisation of neutrophil apoptosis leads to improvement of wound healing and ameliorates symptoms of inflammatory bowel disease.
