Hypertension represents a significant chronic non-infectious disease in China,where Qingda Granule(QDG)has traditionally been employed for its management.However,the mechanisms underlying QDG's kidney protective e...Hypertension represents a significant chronic non-infectious disease in China,where Qingda Granule(QDG)has traditionally been employed for its management.However,the mechanisms underlying QDG's kidney protective effects remain incompletely understood.This study investigates QDG's role in ameliorating hypertensive kidney injury(KI)and elucidates the associated mechanisms.Network analysis identified potential therapeutic targets related to mitochondrial function and the extracellular signal-regulated kinase(ERK)cascade.Ribonucleic acid(RNA)sequencing revealed differentially expressed genes(DEGs)in hypertensive mouse kidneys,which were enriched in mitochondrial-related functions and normalized by QDG treatment.QDG attenuated angiotensin II(Ang II)-induced blood pressure elevation and enhanced renal artery flow.Both cellular and animal experiments demonstrated that QDG inhibits the ERK/ribosomal S6 kinase 1(RSK1)signaling axis,thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis.ERK pathway inhibitors confirmed QDG's mechanism of action through the ERK/RSK1 pathway.These findings indicate that QDG ameliorates hypertensive KI by preserving mitochondrial function through modulation of the ERK/RSK1 network,presenting a novel therapeutic approach for managing hypertensive KI in clinical practice.展开更多
乳腺癌是女性最常见的恶性肿瘤之一。肿瘤的发生、发展是多种基因共同作用的结果。与常染色体上的抑癌基因相比,X染色体连锁的抑癌基因更容易因甲基化或突变等而失活。核糖体S6蛋白激酶4(ribosomal protein S6 kinase4,RSK4)作为一个X...乳腺癌是女性最常见的恶性肿瘤之一。肿瘤的发生、发展是多种基因共同作用的结果。与常染色体上的抑癌基因相比,X染色体连锁的抑癌基因更容易因甲基化或突变等而失活。核糖体S6蛋白激酶4(ribosomal protein S6 kinase4,RSK4)作为一个X染色体连锁基因,可抑制细胞的生长、增殖和分化。RSK4过表达可使细胞增殖下降,使停滞在G_0~G_1期的细胞增加。RSK4可能是乳腺癌的一个与X染色体连锁的抑癌基因。展开更多
基金supported by the National Natural Science Foundation of China(Nos.U22A20372,82204662,82374359,82204662)the Fujian Province Natural Science Foundation(Nos.2022J01369,2021J1942)+1 种基金the Developmental Fund of Chen Keji Integrative Medicine(No.CKJ2022010)the Fujian Natural Science Foundation for Distinguished Young Scholars(No.2024J010032)。
文摘Hypertension represents a significant chronic non-infectious disease in China,where Qingda Granule(QDG)has traditionally been employed for its management.However,the mechanisms underlying QDG's kidney protective effects remain incompletely understood.This study investigates QDG's role in ameliorating hypertensive kidney injury(KI)and elucidates the associated mechanisms.Network analysis identified potential therapeutic targets related to mitochondrial function and the extracellular signal-regulated kinase(ERK)cascade.Ribonucleic acid(RNA)sequencing revealed differentially expressed genes(DEGs)in hypertensive mouse kidneys,which were enriched in mitochondrial-related functions and normalized by QDG treatment.QDG attenuated angiotensin II(Ang II)-induced blood pressure elevation and enhanced renal artery flow.Both cellular and animal experiments demonstrated that QDG inhibits the ERK/ribosomal S6 kinase 1(RSK1)signaling axis,thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis.ERK pathway inhibitors confirmed QDG's mechanism of action through the ERK/RSK1 pathway.These findings indicate that QDG ameliorates hypertensive KI by preserving mitochondrial function through modulation of the ERK/RSK1 network,presenting a novel therapeutic approach for managing hypertensive KI in clinical practice.
文摘乳腺癌是女性最常见的恶性肿瘤之一。肿瘤的发生、发展是多种基因共同作用的结果。与常染色体上的抑癌基因相比,X染色体连锁的抑癌基因更容易因甲基化或突变等而失活。核糖体S6蛋白激酶4(ribosomal protein S6 kinase4,RSK4)作为一个X染色体连锁基因,可抑制细胞的生长、增殖和分化。RSK4过表达可使细胞增殖下降,使停滞在G_0~G_1期的细胞增加。RSK4可能是乳腺癌的一个与X染色体连锁的抑癌基因。