Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartil...Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartilage remains themajor hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding orreversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development isa critical barrier to progress in OA therapy. Recent studies by the current authors’ group and others have revealedthat the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulatesthe expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. Thisreview mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities ofarticular chondrocytes and its implication in the pathogenesis of OA.展开更多
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in men in the Western World. The effects of androgens are mediated by the Androgen Receptor (AR). Therefore, studi...Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in men in the Western World. The effects of androgens are mediated by the Androgen Receptor (AR). Therefore, studies focus on the identification of AR-regulated genes that are also highly expressed in the prostate. STAMP family genes STAMP1/STEAP2 and STAMP2/STEAP4 have only expressed in androgen receptor-positive cells, the role of AR in STAMP family gene expression is an important question. STEAP (Six Transmembrane Epithelial Antigens of Prostate) is the first characterized prostate enriched six transmembrane genes, expressed in metastatic prostate cancer samples, it is tempting to speculate that STAMP/STEAP family genes may be involved in similar functions with a role for both the normal biology and pathophysiology of the prostate. Using siRNA technology in LNCaP cells expressing STAMP genes per se, an apoptosis panel including pro-apoptotic and/or apoptotic molecules was assayed by RT-PCR. In this research project, the prostate-specific STAMP gene family and its regulatory effects on the nuclear factor kappa B and caspase-related pathways were characterized. Considering that the beta-actin response in the control group was high in the immunolabeling studies, an increase in the induction of Tumor Necrosis Factor (TNF) was detected in the signals received with the vital proteins NFkB and akt, which were silenced by siRNA, which means that STAMP genes potentiate vital proteins.展开更多
microRNA(miRNA)is a type of small non-coding RNA that can participate in cell proliferation and apoptosis by regulating gene expression.More and more evidences indicate that miRNA-200a is involved in the occurrence an...microRNA(miRNA)is a type of small non-coding RNA that can participate in cell proliferation and apoptosis by regulating gene expression.More and more evidences indicate that miRNA-200a is involved in the occurrence and development of non-alcoholic fatty liver disease,alcoholic liver disease,drug-induced liver injury,liver fibrosis,and hepatocellular carcinoma.Downstream target genes of serotonin,regulating related signal pathways and playing different roles in the progression of a variety of liver diseases,provide a reference for exploring the mechanism of a variety of chronic liver diseases.展开更多
In Chlamydomonas reinhardtii, the major protease involved in the maintenance of photosynthetic machinery in thylakoid membranes, the FtsH protease, mostly forms large hetero-oligomers (-1 MDa) comprising FtsH1 and F...In Chlamydomonas reinhardtii, the major protease involved in the maintenance of photosynthetic machinery in thylakoid membranes, the FtsH protease, mostly forms large hetero-oligomers (-1 MDa) comprising FtsH1 and FtsH2 subunits, whatever the light intensity for growth. Upon high light exposure, the FtsH subunits display a shorter half-life, which is counterbalanced by an increase in FTSH1/2 mRNA levels, resulting in the modest upregulation of FtsH1/2 proteins. Furthermore, we found that high light increases the protease activity through a hitherto unnoticed redox-controlled reduction of intermolecular disulfide bridges. We iso- lated a Chlamydomonas FTSH1 promoter-deficient mutant, ftsh1-3, resulting from the insertion of a TOC1 transposon, in which the high light-induced upregulation of FTSH1 gene expression is largely lost. In ftsh1- 3, the abundance of FtsH1 and FtsH2 proteins are loosely coupled (decreased by 70% and 30%, respectively) with no formation of large and stable homo-oligomers. Using strains exhibiting different accumulation levels of the FtsH1 subunit after complementation of ftsh1-3, we demonstrate that high light tolerance is tightly correlated with the abundance of the FtsH protease. Thus, the response of Chlamydomonas to light stress involves higher levels of FtsH 1/2 subunits associated into large complexes with increased proteolytic activity.展开更多
基金supported by the United States National Institutes of Health(NIH)under Award Number R01 AR059088(to J.W.)the Mary A.and Paul R.Harrington Distinguished Professorship Endowment.
文摘Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartilage remains themajor hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding orreversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development isa critical barrier to progress in OA therapy. Recent studies by the current authors’ group and others have revealedthat the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulatesthe expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. Thisreview mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities ofarticular chondrocytes and its implication in the pathogenesis of OA.
文摘Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in men in the Western World. The effects of androgens are mediated by the Androgen Receptor (AR). Therefore, studies focus on the identification of AR-regulated genes that are also highly expressed in the prostate. STAMP family genes STAMP1/STEAP2 and STAMP2/STEAP4 have only expressed in androgen receptor-positive cells, the role of AR in STAMP family gene expression is an important question. STEAP (Six Transmembrane Epithelial Antigens of Prostate) is the first characterized prostate enriched six transmembrane genes, expressed in metastatic prostate cancer samples, it is tempting to speculate that STAMP/STEAP family genes may be involved in similar functions with a role for both the normal biology and pathophysiology of the prostate. Using siRNA technology in LNCaP cells expressing STAMP genes per se, an apoptosis panel including pro-apoptotic and/or apoptotic molecules was assayed by RT-PCR. In this research project, the prostate-specific STAMP gene family and its regulatory effects on the nuclear factor kappa B and caspase-related pathways were characterized. Considering that the beta-actin response in the control group was high in the immunolabeling studies, an increase in the induction of Tumor Necrosis Factor (TNF) was detected in the signals received with the vital proteins NFkB and akt, which were silenced by siRNA, which means that STAMP genes potentiate vital proteins.
基金National Natural Science Foundation of China(No.81860790)Guangxi Science and Technology Project(No.Guike AB20297002)+3 种基金Guangxi Natural Science Foundation(No.2020GXNSFAA297160)Guangxi Natural Science Foundation(No.2018GXNSFBA050050)Guangxi First-class Discipline Integrated Traditional Chinese and Western Medicine Cultivation Discipline(No.2019XK159)Guangxi Special Expert Special Project Funding(No.Gui Ren Cai Tong Zi(2019)13)。
文摘microRNA(miRNA)is a type of small non-coding RNA that can participate in cell proliferation and apoptosis by regulating gene expression.More and more evidences indicate that miRNA-200a is involved in the occurrence and development of non-alcoholic fatty liver disease,alcoholic liver disease,drug-induced liver injury,liver fibrosis,and hepatocellular carcinoma.Downstream target genes of serotonin,regulating related signal pathways and playing different roles in the progression of a variety of liver diseases,provide a reference for exploring the mechanism of a variety of chronic liver diseases.
文摘In Chlamydomonas reinhardtii, the major protease involved in the maintenance of photosynthetic machinery in thylakoid membranes, the FtsH protease, mostly forms large hetero-oligomers (-1 MDa) comprising FtsH1 and FtsH2 subunits, whatever the light intensity for growth. Upon high light exposure, the FtsH subunits display a shorter half-life, which is counterbalanced by an increase in FTSH1/2 mRNA levels, resulting in the modest upregulation of FtsH1/2 proteins. Furthermore, we found that high light increases the protease activity through a hitherto unnoticed redox-controlled reduction of intermolecular disulfide bridges. We iso- lated a Chlamydomonas FTSH1 promoter-deficient mutant, ftsh1-3, resulting from the insertion of a TOC1 transposon, in which the high light-induced upregulation of FTSH1 gene expression is largely lost. In ftsh1- 3, the abundance of FtsH1 and FtsH2 proteins are loosely coupled (decreased by 70% and 30%, respectively) with no formation of large and stable homo-oligomers. Using strains exhibiting different accumulation levels of the FtsH1 subunit after complementation of ftsh1-3, we demonstrate that high light tolerance is tightly correlated with the abundance of the FtsH protease. Thus, the response of Chlamydomonas to light stress involves higher levels of FtsH 1/2 subunits associated into large complexes with increased proteolytic activity.