Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previo...Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly inhibits hepatic steatosis and lowers serum triglycerides,playing a protective role against the progression of non-alcoholic fatty liver disease(NAFLD).However,the direct impact of BMP4 on hepatic glucose metabolism is poorly understood.Here,we investigated the regulatory roles of BMP4 in hepatic glucose metabolism.Through a comprehensive analysis of the 14 types of BMPs,we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation,reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism.Mechanistically,we demonstrated that BMP4 reduced the hepatic glucose lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.Collectively,our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism.This knowledge should aid us to understand the molecular pathogenesis of NAFLD,and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.展开更多
Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.A...Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.展开更多
基金The reported study was supported in part by research grants from the 2017 Chongqing Postdoctoral Innovation Talent Support Program(Chongqing Human Resources and Social Security Bureau No.356)(JMF)the 64th China Postdoctoral Science Fund(No.2018M643426)(JMF)+4 种基金the 2019 Chongqing Support Program for Entrepreneurship and Innovation(Chongqing Human Resources and Social Security Bureau No.288)(JMF)the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JMF)the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(CY200409)(JMF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JMF)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906).
文摘Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly inhibits hepatic steatosis and lowers serum triglycerides,playing a protective role against the progression of non-alcoholic fatty liver disease(NAFLD).However,the direct impact of BMP4 on hepatic glucose metabolism is poorly understood.Here,we investigated the regulatory roles of BMP4 in hepatic glucose metabolism.Through a comprehensive analysis of the 14 types of BMPs,we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation,reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism.Mechanistically,we demonstrated that BMP4 reduced the hepatic glucose lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.Collectively,our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism.This knowledge should aid us to understand the molecular pathogenesis of NAFLD,and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.
基金The reported study was supported in part by research grants from the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113)(JF)the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JF)+9 种基金the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(No.CY200409)(JF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JF)and the National Key Research and Development Program of China(2016YFC1000803)RRR,TCH and GAA were partially funded by the National Institutes of Health(DE030480)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430TCH was also supported by the Mabel Green Myers Research Endowment Fund,The University of Chicago Orthopaedics Alumni Fund,and The University of Chicago SHOCK Fund.Funding sources were not involved in the study designin the collection,analysis and/or interpretation of datain the writing of the reportor in the decision to submit the paper for publication.
文摘Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.