Eficiency does not significantly influence myeloid fibroblast activation in the kidney following obstructive injury. A prominent feature of renal interstitial fibrosis is a striking increased production and deposition of extracellular matrix proteins such as collagens and fibronectin. Morphometric analysis of picrosirius red staining of kidney sections at day 14 after obstructive injury demonstrates the presence of interstitial collagen deposition. This collagen deposition is not significantly altered in the obstructed kidneys of IL-6 KO mice. Consistent with these findings, we further illustrate that both WT and IL-6 KO mice display similar increases in collagen I and fibronectin following obstructive injury. These data indicate that IL-6 signaling does not purchase 58-49-1 participate in the regulation extracellular matrix protein production and deposition. In summary, our results demonstrate that IL-6 signaling does not play a significant role in the recruitment of bone marrowThe Role of IL-6 in Renal Fibrosisderived fibroblasts into the kidney and the development of renal fibrosis induced by obstructive injury.Author ContributionsConceived and designed the experiments: YW. Performed the experiments: J Yang JC J Yan GC. Analyzed the data: J Yang JC J Yan GC. Contributed reagents/materials/analysis tools: LZ LH. Wrote the paper: J Yang JC J Yan YW.AcknowledgmentsWe thank Dr. William E. Mitch for helpful discussion. We also thank the flow cytometry core at Baylor College of Medicine and the Innovative Research team at University of Shanghai Municipal Education Commission for 307538-42-7 technical support.
Recent improvements in neonatal intensive care medicine have resulted in marked improvements in the survival of the premature infants [1]. However, bronchopulmonary dysplasia (BPD), a chronic lung disease that follows ventilator and oxygen therapy in the premature infants, still remains a major cause of mortality and morbidity with few effective treatments [2,3]. Although the pathogenesis of BPD has not been clearly elucidate yet, oxidative stress and the ensuing inflammation mediated by neutrophils [4] and pro-inflammatory cytokines [5] is believed to play a seminal role in the lung injury process leading to the development of BPD [6]. Recently, we have shown that local intratracheal but not systemic intraperitoneal xenotransplantation of human umbilical cord blood (UCB)-derived mesenchymal stemcells (MSCs) attenuates hyperoxia induced lung injuries such as impaired alveolarization, increased apoptosis and fibrosis in the immunocompetent neonatal rats [7]. Furthermore, these protective effects of stem cell transplantation were dose dependent [8]. Overall, these findings suggest that human UCB derived MSCs transplantation could be a novel therapeutic modality for BPD. However, while the administration of human UCB-derived MSCs at postnatal day (P) 5 was effective in our previous studies [7,8], the optimal timing for their administration has not been determined yet. Previously, we have shown that the protective effects of human UCB-derived MSCs transplantation are primarily mediated by their anti-inflammatory effects rather than by their regenerative capabilities [7,8]. These findings suggest that the therapeutic timeTiming of MSCs Injection for Hyperoxic Lung Injurywindow of stem cell transplantation could be narrow, i.e., only during the early but not the late phase of inflammatory responses. In the present study, we thus tried to determine the optimal timing at.Eficiency does not significantly influence myeloid fibroblast activation in the kidney following obstructive injury. A prominent feature of renal interstitial fibrosis is a striking increased production and deposition of extracellular matrix proteins such as collagens and fibronectin. Morphometric analysis of picrosirius red staining of kidney sections at day 14 after obstructive injury demonstrates the presence of interstitial collagen deposition. This collagen deposition is not significantly altered in the obstructed kidneys of IL-6 KO mice. Consistent with these findings, we further illustrate that both WT and IL-6 KO mice display similar increases in collagen I and fibronectin following obstructive injury. These data indicate that IL-6 signaling does not participate in the regulation extracellular matrix protein production and deposition. In summary, our results demonstrate that IL-6 signaling does not play a significant role in the recruitment of bone marrowThe Role of IL-6 in Renal Fibrosisderived fibroblasts into the kidney and the development of renal fibrosis induced by obstructive injury.Author ContributionsConceived and designed the experiments: YW. Performed the experiments: J Yang JC J Yan GC. Analyzed the data: J Yang JC J Yan GC. Contributed reagents/materials/analysis tools: LZ LH. Wrote the paper: J Yang JC J Yan YW.AcknowledgmentsWe thank Dr. William E. Mitch for helpful discussion. We also thank the flow cytometry core at Baylor College of Medicine and the Innovative Research team at University of Shanghai Municipal Education Commission for technical support.
Recent improvements in neonatal intensive care medicine have resulted in marked improvements in the survival of the premature infants [1]. However, bronchopulmonary dysplasia (BPD), a chronic lung disease that follows ventilator and oxygen therapy in the premature infants, still remains a major cause of mortality and morbidity with few effective treatments [2,3]. Although the pathogenesis of BPD has not been clearly elucidate yet, oxidative stress and the ensuing inflammation mediated by neutrophils [4] and pro-inflammatory cytokines [5] is believed to play a seminal role in the lung injury process leading to the development of BPD [6]. Recently, we have shown that local intratracheal but not systemic intraperitoneal xenotransplantation of human umbilical cord blood (UCB)-derived mesenchymal stemcells (MSCs) attenuates hyperoxia induced lung injuries such as impaired alveolarization, increased apoptosis and fibrosis in the immunocompetent neonatal rats [7]. Furthermore, these protective effects of stem cell transplantation were dose dependent [8]. Overall, these findings suggest that human UCB derived MSCs transplantation could be a novel therapeutic modality for BPD. However, while the administration of human UCB-derived MSCs at postnatal day (P) 5 was effective in our previous studies [7,8], the optimal timing for their administration has not been determined yet. Previously, we have shown that the protective effects of human UCB-derived MSCs transplantation are primarily mediated by their anti-inflammatory effects rather than by their regenerative capabilities [7,8]. These findings suggest that the therapeutic timeTiming of MSCs Injection for Hyperoxic Lung Injurywindow of stem cell transplantation could be narrow, i.e., only during the early but not the late phase of inflammatory responses. In the present study, we thus tried to determine the optimal timing at.
