The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Craig K Kent - One of the best experts on this subject based on the ideXlab platform.
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preferential secretion of Collagen Type 3 versus Type 1 from adventitial fibroblasts stimulated by tgf β smad3 treated medial smooth muscle cells
Cellular Signalling, 2013Co-Authors: Shakti A Goel, Rishi Kundi, Gregory Sovinski, Stephen Seedial, Craig K KentAbstract:Abstract Restenosis, or arterial lumen re-narrowing, occurs in 30–50% of the patients undergoing angioplasty. Adaptive remodeling is the compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total Collagen in the adventitia. In order to gain insights into a possible role of Collagen in Smad3-induced adaptive remodeling, here we have investigated a mechanism of cell–cell communication between medial smooth muscle cells (SMCs) and adventitial fibroblasts in regulating the secretion of two major Collagen subTypes. We have identified a preferential Collagen-3 versus Collagen-1 secretion by adventitial fibroblasts following stimulation by the conditioned medium from the TGF-β1-treated/Smad3-expressing medial smooth muscle cells (SMCs), which contained higher levels of CTGF and IGF2 as compared to control medium. Treating the TGF-β/Smad3-stimulated SMCs with an siRNA to either CTGF or IGF2 reversed the effect of conditioned media on preferential Collagen-3 secretion from fibroblasts. Moreover, recombinant CTGF and IGF2 together stimulated adventitial fibroblasts to preferentially secrete Collagen-3 versus Collagen-1. This is the first study to identify a preferential secretion of Collagen-3 versus Collagen-1 from adventitial fibroblasts as a result of TGF-β/Smad3 stimulation of medial SMCs, and that CTGF and IGF2 function together to mediate this signaling communication between the two cell Types.
Shakti A Goel - One of the best experts on this subject based on the ideXlab platform.
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preferential secretion of Collagen Type 3 versus Type 1 from adventitial fibroblasts stimulated by tgf β smad3 treated medial smooth muscle cells
Cellular Signalling, 2013Co-Authors: Shakti A Goel, Rishi Kundi, Gregory Sovinski, Stephen Seedial, Craig K KentAbstract:Abstract Restenosis, or arterial lumen re-narrowing, occurs in 30–50% of the patients undergoing angioplasty. Adaptive remodeling is the compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total Collagen in the adventitia. In order to gain insights into a possible role of Collagen in Smad3-induced adaptive remodeling, here we have investigated a mechanism of cell–cell communication between medial smooth muscle cells (SMCs) and adventitial fibroblasts in regulating the secretion of two major Collagen subTypes. We have identified a preferential Collagen-3 versus Collagen-1 secretion by adventitial fibroblasts following stimulation by the conditioned medium from the TGF-β1-treated/Smad3-expressing medial smooth muscle cells (SMCs), which contained higher levels of CTGF and IGF2 as compared to control medium. Treating the TGF-β/Smad3-stimulated SMCs with an siRNA to either CTGF or IGF2 reversed the effect of conditioned media on preferential Collagen-3 secretion from fibroblasts. Moreover, recombinant CTGF and IGF2 together stimulated adventitial fibroblasts to preferentially secrete Collagen-3 versus Collagen-1. This is the first study to identify a preferential secretion of Collagen-3 versus Collagen-1 from adventitial fibroblasts as a result of TGF-β/Smad3 stimulation of medial SMCs, and that CTGF and IGF2 function together to mediate this signaling communication between the two cell Types.
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Preferential secretion of Collagen Type 3 versus Type 1 from adventitial fibroblasts stimulated by TGF-β/Smad3-treated medial smooth muscle cells
Cellular Signalling, 2012Co-Authors: Shakti A Goel, Rishi Kundi, Gregory Sovinski, Stephen Seedial, K. Craig KentAbstract:Abstract Restenosis, or arterial lumen re-narrowing, occurs in 30–50% of the patients undergoing angioplasty. Adaptive remodeling is the compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total Collagen in the adventitia. In order to gain insights into a possible role of Collagen in Smad3-induced adaptive remodeling, here we have investigated a mechanism of cell–cell communication between medial smooth muscle cells (SMCs) and adventitial fibroblasts in regulating the secretion of two major Collagen subTypes. We have identified a preferential Collagen-3 versus Collagen-1 secretion by adventitial fibroblasts following stimulation by the conditioned medium from the TGF-β1-treated/Smad3-expressing medial smooth muscle cells (SMCs), which contained higher levels of CTGF and IGF2 as compared to control medium. Treating the TGF-β/Smad3-stimulated SMCs with an siRNA to either CTGF or IGF2 reversed the effect of conditioned media on preferential Collagen-3 secretion from fibroblasts. Moreover, recombinant CTGF and IGF2 together stimulated adventitial fibroblasts to preferentially secrete Collagen-3 versus Collagen-1. This is the first study to identify a preferential secretion of Collagen-3 versus Collagen-1 from adventitial fibroblasts as a result of TGF-β/Smad3 stimulation of medial SMCs, and that CTGF and IGF2 function together to mediate this signaling communication between the two cell Types.
Job C. Tharappel - One of the best experts on this subject based on the ideXlab platform.
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Hernia Repair Strength Enhanced With Antioxidants.
Journal of Surgical Research, 2019Co-Authors: Vashisht Madabhushi, Job C. Tharappel, Satya Alluri, Crystal F. Totten, John Scott RothAbstract:Abstract Background Incisional hernia is one of the most common complications of abdominal surgery, and repairs are associated with significant recurrence rates. Mesh repairs are associated with the best outcomes, but failures are not uncommon. Doxycycline has been demonstrated to enhance mesh hernia repair outcomes with associated increases in Collagen deposition and improved tensiometric strength. This study compares the outcomes of incisional hernia repair with doxycycline administration and the antioxidant tempol. Materials and methods Twenty-eight male Sprague Dawley rats underwent a midline hernia creation and an intraabdominal polypropylene mesh repair. The animals were administered saline, doxycycline, tempol, or both, daily for 8 wk. The abdominal wall was harvested at 8 wk and tensiometric strength and biochemical analysis was performed. Results The tensiometric strength of the repair was increased in all experimental groups. Collagen Type 1 deposition was increased, and Collagen Type 3 deposition was decreased in each of the experimental groups relative to control. There was no difference in MMP-2 and MMP-9 levels between control and experimental groups. Conclusions The hernia repair strength is equally enhanced with the administration of doxycycline or tempol. Dual therapy provided no benefit over treatment with either single agent. All treatment groups had an increase in Collagen Type 1:3 ratios, but the mechanism is not well understood. The benefits of antioxidant treatment following hernia repair are similar to treatment with doxycycline. Given the high frequency of incisional hernia repair failures, this study has implications for improving outcomes following ventral hernia repair through the use of either doxycycline or antioxidant therapy.
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Doxycycline alters Collagen composition following ventral hernia repair
Surgical Endoscopy, 2017Co-Authors: Job C. Tharappel, Crystal F. Totten, Jennifer W. Harris, Brittany A. Zwischenberger, John Scott RothAbstract:Background Doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been demonstrated to impact the strength of the polypropylene (PP) mesh-repaired hernia with an increase in the deposition of Collagen Type 1. The impact of doxycycline with porcine acellular dermal matrices (PADM) is unknown; therefore, we evaluated the impact of doxycycline administration upon hernia repair with PP and PADM mesh. Methods Sprague–Dawley rats weighing ~400 g underwent laparotomy with creation of a midline ventral hernia. After a 27-day recovery, animals were randomly assigned to four groups of eight and underwent intraperitoneal underlay hernia repair with either PP or PADM. Groups were assigned to daily normal saline (S) or daily doxycycline in normal saline 10 mg/kg (D) via oral gavage for 8 weeks beginning 24 h preoperatively. Animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall and western blot analyses for Collagen subTypes and MMPs. Results Thirty-two animals underwent successful hernia creation and repair with either PADM or PP. At 8 weeks, 15 of 16 PP-implanted animals survived with only 12 of 16 PADM-implanted animals surviving. There were no differences in the mesh to fascial interface tensiometric strength between groups. Densitometric counts in the PADM-D group demonstrated increased Collagen Type 1 compared to PP-S (PADM-D [1286.5], PADM-S [906.9], PP-S [700.4], p = 0.037) and decreased Collagen Type 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11,297.1], p = 0.01). MMP-9 levels were increased in PADM-D (PP-S vs. PADM-D, p = 0.04), while MMP-2 levels were similar between PADM-D and PADM-S, respectively. Conclusions Collagen Type 1 deposition at the mesh to fascial interface is enhanced following administration of doxycycline in ventral hernia repairs with porcine acellular dermal matrices. Doxycycline administration may have implications for enhancing hernia repair outcomes using biologic mesh.
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Doxycycline alters Collagen composition following ventral hernia repair
Surgical Endoscopy and Other Interventional Techniques, 2016Co-Authors: Job C. Tharappel, Crystal F. Totten, Jennifer W. Harris, Brittany A. Zwischenberger, John Scott RothAbstract:Doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been demonstrated to impact the strength of the polypropylene (PP) mesh-repaired hernia with an increase in the deposition of Collagen Type 1. The impact of doxycycline with porcine acellular dermal matrices (PADM) is unknown; therefore, we evaluated the impact of doxycycline administration upon hernia repair with PP and PADM mesh. Sprague–Dawley rats weighing ~400 g underwent laparotomy with creation of a midline ventral hernia. After a 27-day recovery, animals were randomly assigned to four groups of eight and underwent intraperitoneal underlay hernia repair with either PP or PADM. Groups were assigned to daily normal saline (S) or daily doxycycline in normal saline 10 mg/kg (D) via oral gavage for 8 weeks beginning 24 h preoperatively. Animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall and western blot analyses for Collagen subTypes and MMPs. Thirty-two animals underwent successful hernia creation and repair with either PADM or PP. At 8 weeks, 15 of 16 PP-implanted animals survived with only 12 of 16 PADM-implanted animals surviving. There were no differences in the mesh to fascial interface tensiometric strength between groups. Densitometric counts in the PADM-D group demonstrated increased Collagen Type 1 compared to PP-S (PADM-D [1286.5], PADM-S [906.9], PP-S [700.4], p = 0.037) and decreased Collagen Type 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11,297.1], p = 0.01). MMP-9 levels were increased in PADM-D (PP-S vs. PADM-D, p = 0.04), while MMP-2 levels were similar between PADM-D and PADM-S, respectively. Collagen Type 1 deposition at the mesh to fascial interface is enhanced following administration of doxycycline in ventral hernia repairs with porcine acellular dermal matrices. Doxycycline administration may have implications for enhancing hernia repair outcomes using biologic mesh.
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Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair
Surgical Endoscopy, 2016Co-Authors: Job C. Tharappel, Jennifer W. Harris, Brittany A. Zwischenberger, Salomon M. Levy, David A. Puleo, J. Scott RothAbstract:Background Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats. Study design Fifty-six Sprague-Dawley rats underwent hernia repair with either PP mesh ( n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and Collagen Type 1 and 3 were analyzed by western blotting. Results In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in Collagen 1 and significant reduction in Collagen Type 3 when compared to control. Conclusion It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings.
John Scott Roth - One of the best experts on this subject based on the ideXlab platform.
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Hernia Repair Strength Enhanced With Antioxidants.
Journal of Surgical Research, 2019Co-Authors: Vashisht Madabhushi, Job C. Tharappel, Satya Alluri, Crystal F. Totten, John Scott RothAbstract:Abstract Background Incisional hernia is one of the most common complications of abdominal surgery, and repairs are associated with significant recurrence rates. Mesh repairs are associated with the best outcomes, but failures are not uncommon. Doxycycline has been demonstrated to enhance mesh hernia repair outcomes with associated increases in Collagen deposition and improved tensiometric strength. This study compares the outcomes of incisional hernia repair with doxycycline administration and the antioxidant tempol. Materials and methods Twenty-eight male Sprague Dawley rats underwent a midline hernia creation and an intraabdominal polypropylene mesh repair. The animals were administered saline, doxycycline, tempol, or both, daily for 8 wk. The abdominal wall was harvested at 8 wk and tensiometric strength and biochemical analysis was performed. Results The tensiometric strength of the repair was increased in all experimental groups. Collagen Type 1 deposition was increased, and Collagen Type 3 deposition was decreased in each of the experimental groups relative to control. There was no difference in MMP-2 and MMP-9 levels between control and experimental groups. Conclusions The hernia repair strength is equally enhanced with the administration of doxycycline or tempol. Dual therapy provided no benefit over treatment with either single agent. All treatment groups had an increase in Collagen Type 1:3 ratios, but the mechanism is not well understood. The benefits of antioxidant treatment following hernia repair are similar to treatment with doxycycline. Given the high frequency of incisional hernia repair failures, this study has implications for improving outcomes following ventral hernia repair through the use of either doxycycline or antioxidant therapy.
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Doxycycline alters Collagen composition following ventral hernia repair
Surgical Endoscopy, 2017Co-Authors: Job C. Tharappel, Crystal F. Totten, Jennifer W. Harris, Brittany A. Zwischenberger, John Scott RothAbstract:Background Doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been demonstrated to impact the strength of the polypropylene (PP) mesh-repaired hernia with an increase in the deposition of Collagen Type 1. The impact of doxycycline with porcine acellular dermal matrices (PADM) is unknown; therefore, we evaluated the impact of doxycycline administration upon hernia repair with PP and PADM mesh. Methods Sprague–Dawley rats weighing ~400 g underwent laparotomy with creation of a midline ventral hernia. After a 27-day recovery, animals were randomly assigned to four groups of eight and underwent intraperitoneal underlay hernia repair with either PP or PADM. Groups were assigned to daily normal saline (S) or daily doxycycline in normal saline 10 mg/kg (D) via oral gavage for 8 weeks beginning 24 h preoperatively. Animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall and western blot analyses for Collagen subTypes and MMPs. Results Thirty-two animals underwent successful hernia creation and repair with either PADM or PP. At 8 weeks, 15 of 16 PP-implanted animals survived with only 12 of 16 PADM-implanted animals surviving. There were no differences in the mesh to fascial interface tensiometric strength between groups. Densitometric counts in the PADM-D group demonstrated increased Collagen Type 1 compared to PP-S (PADM-D [1286.5], PADM-S [906.9], PP-S [700.4], p = 0.037) and decreased Collagen Type 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11,297.1], p = 0.01). MMP-9 levels were increased in PADM-D (PP-S vs. PADM-D, p = 0.04), while MMP-2 levels were similar between PADM-D and PADM-S, respectively. Conclusions Collagen Type 1 deposition at the mesh to fascial interface is enhanced following administration of doxycycline in ventral hernia repairs with porcine acellular dermal matrices. Doxycycline administration may have implications for enhancing hernia repair outcomes using biologic mesh.
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Doxycycline alters Collagen composition following ventral hernia repair
Surgical Endoscopy and Other Interventional Techniques, 2016Co-Authors: Job C. Tharappel, Crystal F. Totten, Jennifer W. Harris, Brittany A. Zwischenberger, John Scott RothAbstract:Doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been demonstrated to impact the strength of the polypropylene (PP) mesh-repaired hernia with an increase in the deposition of Collagen Type 1. The impact of doxycycline with porcine acellular dermal matrices (PADM) is unknown; therefore, we evaluated the impact of doxycycline administration upon hernia repair with PP and PADM mesh. Sprague–Dawley rats weighing ~400 g underwent laparotomy with creation of a midline ventral hernia. After a 27-day recovery, animals were randomly assigned to four groups of eight and underwent intraperitoneal underlay hernia repair with either PP or PADM. Groups were assigned to daily normal saline (S) or daily doxycycline in normal saline 10 mg/kg (D) via oral gavage for 8 weeks beginning 24 h preoperatively. Animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall and western blot analyses for Collagen subTypes and MMPs. Thirty-two animals underwent successful hernia creation and repair with either PADM or PP. At 8 weeks, 15 of 16 PP-implanted animals survived with only 12 of 16 PADM-implanted animals surviving. There were no differences in the mesh to fascial interface tensiometric strength between groups. Densitometric counts in the PADM-D group demonstrated increased Collagen Type 1 compared to PP-S (PADM-D [1286.5], PADM-S [906.9], PP-S [700.4], p = 0.037) and decreased Collagen Type 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11,297.1], p = 0.01). MMP-9 levels were increased in PADM-D (PP-S vs. PADM-D, p = 0.04), while MMP-2 levels were similar between PADM-D and PADM-S, respectively. Collagen Type 1 deposition at the mesh to fascial interface is enhanced following administration of doxycycline in ventral hernia repairs with porcine acellular dermal matrices. Doxycycline administration may have implications for enhancing hernia repair outcomes using biologic mesh.
Rishi Kundi - One of the best experts on this subject based on the ideXlab platform.
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preferential secretion of Collagen Type 3 versus Type 1 from adventitial fibroblasts stimulated by tgf β smad3 treated medial smooth muscle cells
Cellular Signalling, 2013Co-Authors: Shakti A Goel, Rishi Kundi, Gregory Sovinski, Stephen Seedial, Craig K KentAbstract:Abstract Restenosis, or arterial lumen re-narrowing, occurs in 30–50% of the patients undergoing angioplasty. Adaptive remodeling is the compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total Collagen in the adventitia. In order to gain insights into a possible role of Collagen in Smad3-induced adaptive remodeling, here we have investigated a mechanism of cell–cell communication between medial smooth muscle cells (SMCs) and adventitial fibroblasts in regulating the secretion of two major Collagen subTypes. We have identified a preferential Collagen-3 versus Collagen-1 secretion by adventitial fibroblasts following stimulation by the conditioned medium from the TGF-β1-treated/Smad3-expressing medial smooth muscle cells (SMCs), which contained higher levels of CTGF and IGF2 as compared to control medium. Treating the TGF-β/Smad3-stimulated SMCs with an siRNA to either CTGF or IGF2 reversed the effect of conditioned media on preferential Collagen-3 secretion from fibroblasts. Moreover, recombinant CTGF and IGF2 together stimulated adventitial fibroblasts to preferentially secrete Collagen-3 versus Collagen-1. This is the first study to identify a preferential secretion of Collagen-3 versus Collagen-1 from adventitial fibroblasts as a result of TGF-β/Smad3 stimulation of medial SMCs, and that CTGF and IGF2 function together to mediate this signaling communication between the two cell Types.
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Preferential secretion of Collagen Type 3 versus Type 1 from adventitial fibroblasts stimulated by TGF-β/Smad3-treated medial smooth muscle cells
Cellular Signalling, 2012Co-Authors: Shakti A Goel, Rishi Kundi, Gregory Sovinski, Stephen Seedial, K. Craig KentAbstract:Abstract Restenosis, or arterial lumen re-narrowing, occurs in 30–50% of the patients undergoing angioplasty. Adaptive remodeling is the compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total Collagen in the adventitia. In order to gain insights into a possible role of Collagen in Smad3-induced adaptive remodeling, here we have investigated a mechanism of cell–cell communication between medial smooth muscle cells (SMCs) and adventitial fibroblasts in regulating the secretion of two major Collagen subTypes. We have identified a preferential Collagen-3 versus Collagen-1 secretion by adventitial fibroblasts following stimulation by the conditioned medium from the TGF-β1-treated/Smad3-expressing medial smooth muscle cells (SMCs), which contained higher levels of CTGF and IGF2 as compared to control medium. Treating the TGF-β/Smad3-stimulated SMCs with an siRNA to either CTGF or IGF2 reversed the effect of conditioned media on preferential Collagen-3 secretion from fibroblasts. Moreover, recombinant CTGF and IGF2 together stimulated adventitial fibroblasts to preferentially secrete Collagen-3 versus Collagen-1. This is the first study to identify a preferential secretion of Collagen-3 versus Collagen-1 from adventitial fibroblasts as a result of TGF-β/Smad3 stimulation of medial SMCs, and that CTGF and IGF2 function together to mediate this signaling communication between the two cell Types.