Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Connective tissue growth factor(CTGF),a multifunctional protein of the CCN family,regulates cell proliferation,differentiation,adhesion,and a variety of other biological processes.It is involved in the disease-related...Connective tissue growth factor(CTGF),a multifunctional protein of the CCN family,regulates cell proliferation,differentiation,adhesion,and a variety of other biological processes.It is involved in the disease-related pathways such as the Hippo pathway,p53 and nuclear factor kappa-B(NF-κB)pathways and thus contributes to the developments of inflammation,fibrosis,cancer and other diseases as a downstream effector.Therefore,CTGF might be a potential therapeutic target for treating various diseases.In recent years,the research on the potential of CTGF in the treatment of diseases has also been paid more attention.Several drugs targeting CTGF(monoclonal antibodies FG3149 and FG3019)are being assessed by clinical or preclinical trials and have shown promising outcomes.In this review,the cellular events regulated by CTGF,and the relationships between CTGF and pathogenesis of diseases are systematically summarized.In addition,we highlight the current researches,focusing on the preclinical and clinical trials concerned with CTGF as the therapeutic target.展开更多
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
基金This work is supported by the National Science Foundation for Excellent Young Scholars(32122052,China)National Natural Science Foundation Regional Innovation and Development(No.U19A2003,China).
文摘Connective tissue growth factor(CTGF),a multifunctional protein of the CCN family,regulates cell proliferation,differentiation,adhesion,and a variety of other biological processes.It is involved in the disease-related pathways such as the Hippo pathway,p53 and nuclear factor kappa-B(NF-κB)pathways and thus contributes to the developments of inflammation,fibrosis,cancer and other diseases as a downstream effector.Therefore,CTGF might be a potential therapeutic target for treating various diseases.In recent years,the research on the potential of CTGF in the treatment of diseases has also been paid more attention.Several drugs targeting CTGF(monoclonal antibodies FG3149 and FG3019)are being assessed by clinical or preclinical trials and have shown promising outcomes.In this review,the cellular events regulated by CTGF,and the relationships between CTGF and pathogenesis of diseases are systematically summarized.In addition,we highlight the current researches,focusing on the preclinical and clinical trials concerned with CTGF as the therapeutic target.