Dataset Information

Based on HIF-1α/Wnt/β-Catenin Pathway to Explore the Effect of Qingshen Granules on Chronic Renal Failure Patients: A Randomized Controlled Trial.

ABSTRACT: Objectives. This study investigates the effect of Qingshen Granules (QSG) on chronic renal failure patients and the HIF-1α/Wnt/β-catenin signaling pathway. Methods. Subjects were randomly divided into treatment and control groups, with 42 patients in each group. Participants in the treatment group received 10 g oral doses of QSG 3 times a day, for 12 weeks, whereas subjects in the control group were given a placebo. The effective rates of traditional Chinese medicine (TCM) symptom, serum creatinine (Scr), and estimate glomerular filtration rate (eGFR) as well as the serum levels of HIF-1α, Wnt1, β-catenin, α-SMA, and E-cadherin were evaluated. Results. Eighty patients completed the treatment program and two dropped out. After 12 weeks, the effective rates of TCM symptom and eGFR were found to be higher in the treatment group than in the control group, with statistically significant differences (P = 0.024 and 0.019, respectively). Meanwhile, lower levels of HIF-1α, Wnt1, β-catenin, α-SMA, and E-cadherin were detected in the treatment group, and the differences were statistically significant (P ≤ 0.001, P = 0.001, P ≤ 0.001, P ≤ 0.001, and P = 0.039). No adverse events occurred during the study. Conclusions. QSG can alleviate the clinical symptoms of chronic renal failure (CRF) and protect renal function in patients by influencing the HIF-1α/Wnt/β-catenin signaling pathway. The treatment exhibits no adverse effects and is thus safe to be used by humans.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6633969 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Based on HIF-1α/Wnt/β-Catenin Pathway to Explore the Effect of Qingshen Granules on Chronic Renal Failure Patients: A Randomized Controlled Trial.

Wang Yiping Y Zhang Lei L Jin Hua H Wang Dong D

Evidence-based complementary and alternative medicine : eCAM 20190702

Objectives. This study investigates the effect of Qingshen Granules (QSG) on chronic renal failure patients and the HIF-1α/Wnt/β-catenin signaling pathway. Methods. Subjects were randomly divided into treatment and control groups, with 42 patients in each group. Participants in the treatment group received 10 g oral doses of QSG 3 times a day, for 12 weeks, whereas subjects in the control group were given a placebo. The effective rates of traditional Chinese medicine ...[more]

PMID: 31354858

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Project description:The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic lung diseases, such as Idiopathic Pulmonary Fibrosis (IPF). Cellular senescence is a major hallmark of aging and has a higher occurrence in IPF. The lung epithelium represents a major site of tissue injury, cellular senescence and aberrant activity of developmental pathways such as the WNT/β-catenin pathway in IPF. The potential impact of WNT/β-catenin signaling on alveolar epithelial senescence in general as well as in IPF, however, remains elusive. Here, we characterized alveolar epithelial cells of aged mice and assessed the contribution of chronic WNT/β-catenin signaling on alveolar epithelial type (AT) II cell senescence. Whole lungs from old (16-24 months) versus young (3 months) mice had relatively less epithelial (EpCAM+) but more inflammatory (CD45+) cells, as assessed by flow cytometry. Compared to young ATII cells, old ATII cells showed decreased expression of the ATII cell marker Surfactant Protein C along with increased expression of the ATI cell marker Hopx, accompanied by increased WNT/β-catenin activity. Notably, when placed in an organoid assay, old ATII cells exhibited decreased progenitor cell potential. Chronic canonical WNT/β-catenin activation for up to 7 days in primary ATII cells as well as alveolar epithelial cell lines induced a robust cellular senescence, whereas the non-canonical ligand WNT5A was not able to induce cellular senescence. Moreover, chronic WNT3A treatment of precision-cut lung slices (PCLS) further confirmed ATII cell senescence. Simultaneously, chronic but not acute WNT/β-catenin activation induced a profibrotic state with increased expression of the impaired ATII cell marker Keratin 8. These results suggest that chronic WNT/β-catenin activity in the IPF lung contributes to increased ATII cell senescence and reprogramming. In the fibrotic environment, WNT/β-catenin signaling thus might lead to further progenitor cell dysfunction and impaired lung repair.

Project description:BackgroundHypoxia naturally happens in embryogenesis and thus serves as an important environmental factor affecting embryo development. Hif-1α, an essential hypoxia response factor, was mostly considered to mediate or synergistically regulate the effect of hypoxia on stem cells. However, the function and relationship of hypoxia and Hif-1α in regulating mesendoderm differentiation remains controversial.ResultsWe here discovered that hypoxia dramatically suppressed the mesendoderm differentiation and promoted the ectoderm differentiation of mouse embryonic stem cells (mESCs). However, hypoxia treatment after mesendoderm was established promoted the downstream differentiation of mesendoderm-derived lineages. These effects of hypoxia were mediated by the repression of the Wnt/β-Catenin pathway and the Wnt/β-Catenin pathway was at least partially regulated by the Akt/Gsk3β axis. Blocking the Wnt/β-Catenin pathway under normoxia using IWP2 mimicked the effects of hypoxia while activating the Wnt/β-Catenin pathway with CHIR99021 fully rescued the mesendoderm differentiation suppression caused by hypoxia. Unexpectedly, Hif-1α overexpression, in contrast to hypoxia, promoted mesendoderm differentiation and suppressed ectoderm differentiation. Knockdown of Hif-1α under normoxia and hypoxia both inhibited the mesendoderm differentiation. Moreover, hypoxia even suppressed the mesendoderm differentiation of Hif-1α knockdown mESCs, further implying that the effects of hypoxia on the mesendoderm differentiation were Hif-1α independent. Consistently, the Wnt/β-Catenin pathway was enhanced by Hif-1α overexpression and inhibited by Hif-1α knockdown. As shown by RNA-seq, unlike hypoxia, the effect of Hif-1α was relatively mild and selectively regulated part of hypoxia response genes, which fine-tuned the effect of hypoxia on mESC differentiation.ConclusionsThis study revealed that hypoxia is fine-tuned by Hif-1α and regulates the mesendoderm and ectoderm differentiation by manipulating the Wnt/β-Catenin pathway, which contributed to the understanding of hypoxia-mediated regulation of development.

Dataset Information

Based on HIF-1α/Wnt/β-Catenin Pathway to Explore the Effect of Qingshen Granules on Chronic Renal Failure Patients: A Randomized Controlled Trial.

Publications

Based on HIF-1<i>α</i>/Wnt/<i>β</i>-Catenin Pathway to Explore the Effect of Qingshen Granules on Chronic Renal Failure Patients: A Randomized Controlled Trial.

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