Thymosin β4 suppresses CCl<sub>4</sub>‐induced murine hepatic fibrosis by down‐regulating transforming growth factor β receptor‐II

Li, Hanchao; Li, Qian; Zhang, Xueting; Zheng, Xiaoyan; Zhang, Qiannan; Hao, Zhiming

doi:10.1002/jgm.3043

Cited by 12 publications

(10 citation statements)

References 44 publications

(97 reference statements)

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“…It protects against cardiac, kidney and corneal injury [53] . Herein, in agreement with the previous studies in which systemic T β 4 administration decreased the TNF-α level in mice with sepsis and with experimental colitis as well [54,55] , the present study demonstrated that T β 4 significantly reduced the elevated tissue TNF-α and IL-6 levels in the intestinal I/R injury group suggesting restoration of the balance of proinflammatory cytokines confirming the potential anti-inflammatory effect of Tβ4 in attenuating the intestinal I/R injury.…”

Section: Discussionsupporting

confidence: 92%

Thymosin Beta 4 Improves the Intestinal Ischemia/Reperfusion Injury in Rats

kattawy¹,

Abozaid²

2020

Am. J. Biomed. Sci.

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Background and purpose: Intestinal ischemia-reperfusion (I/R) injury is a common clinical issue involving sepsis, shock, necrotizing enterocolitis, mesenteric thrombosis. Inflammatory reactions and cellular apoptosis are mainly involved processes in intestinal I/R injury. Data regarding the effect of thymosin beta 4 (Tβ4) on intestinal I/R injury are scarce. It was designed to evaluate the potential effects of Tβ4 on intestinal IR injury.Methods: The study was conducted on 3 groups of adult male albino rats: each containing ten rats: group I (I/R group), group II (Sham-operated group), and group III (Tβ4-treated group). After one hour of intestinal ischemia, reperfusion was performed by releasing the clamp. Thirty minutes before reperfusion, the rats in group III received subcutaneous injections of 30 mg Tβ4 per kg and 0.1 ml physiologic saline. Rats in groups I and II received only 0.1 ml physiologic saline. Intestinal histopathologic examination and scoring the degree of injury were done according to chiu's score. Biochemical analyses of malondialdehyde (MDA), super oxide dismutase (SOD) and glutathione peroxidase (Gpx) levels in addition to TNF-α , IL-6 and caspase-3 levels in the rat intestinal tissues were determined. Serum and tissue nitric oxide (NO) levels were also measured.Results: Intestinal I/R injury was confirmed by intestinal histopathologic examination. In the I/R group, tissue MDA, TNF-α , IL-6 and caspase-3 levels were significantly elevated, however, tissue SOD, Gpx, serum and tissue NO levels were significantly declined when compared to the sham group. On receiving Tβ 4, the findings demonstrated significant reductions of tissue MDA, TNF-α, IL-6 and caspase-3 levels and significant elevations of serum and tissue NO, tissue SOD and Gpx levels compared to non-treated one. Further, rats treated with Tβ4 showed amelioration of the degree of intestinal I/R lesions and improvement of intestinal score injury compared to non-treated group.

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Section: Discussionsupporting

confidence: 92%

Thymosin Beta 4 Improves the Intestinal Ischemia/Reperfusion Injury in Rats

kattawy¹,

Abozaid²

2020

Am. J. Biomed. Sci.

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“…To localize TMSB4X in the E15 chick utricle, we used an antibody that has been validated previously with knock-down experiments against mouse TMSB4X (Zhou et al, 2013; Li et al, 2018); chicken TMSB4X differs from mouse and human TMSB4X by only two serine-to-threonine substitutions out of 44 total amino acids. TMSB4X immunoreactivity was cytoplasmic and strong in supporting cells and substantially reduced in hair cells (Figure 3G–I and Figure 3—figure supplement 3), which was consistent with the mass-spectrometry results.…”

Section: Resultsmentioning

confidence: 99%

Single-cell proteomics reveals changes in expression during hair-cell development

Zhu

Scheibinger

Ellwanger

et al. 2019

eLife

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Hearing and balance rely on small sensory hair cells that reside in the inner ear. To explore dynamic changes in the abundant proteins present in differentiating hair cells, we used nanoliter-scale shotgun mass spectrometry of single cells, each ~1 picoliter, from utricles of embryonic day 15 chickens. We identified unique constellations of proteins or protein groups from presumptive hair cells and from progenitor cells. The single-cell proteomes enabled the de novo reconstruction of a developmental trajectory using protein expression levels, revealing proteins that greatly increased in expression during differentiation of hair cells (e.g., OCM, CRABP1, GPX2, AK1, GSTO1) and those that decreased during differentiation (e.g., TMSB4X, AGR3). Complementary single-cell transcriptome profiling showed corresponding changes in mRNA during maturation of hair cells. Single-cell proteomics data thus can be mined to reveal features of cellular development that may be missed with transcriptomics.

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“…TGF-β is a central mediator of the liver brosis process, activating transdi erentiation from HSCs to myo broblasts and producing ECM. Previous animal studies demonstrated that hepatic TGF-β overexpression increased brosis, whereas TGF-β neutralization abolished this process [34][35][36]. erefore, anti-TGF-β strategies have been developed to treat chronic liver diseases [37].…”

Section: Discussionmentioning

confidence: 99%

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-β1 in Wistar Rats

Jia

Zheng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Shi-Wei-Gan-Ning-San (SWGNS) is a classic Tibetan prescription, which has obvious clinical effects in the treatment of viral hepatitis, fatty liver, liver fibrosis, liver cirrhosis, liver cancer, and other liver injuries. However, animal studies and mechanism studies are still lacking. This study aimed to investigate its hepatoprotective efficacy and pharmacological mechanism in animal experiments. Methods. Chronic liver injury was induced by oral administration of carbon tetrachloride (CCl4) in Wistar rats for 13 weeks. SWGNS was administered orally to rats at doses of 235, 705, and 1410 mg/kg for 13 weeks. Blood samples were collected for biochemical, ELISA, and radioimmunoassay. Livers were harvested for H&E and immunohistochemical staining. The major constituents of SWGNS were analyzed by HPLC. In vitro experiments were used to explore the protective effect of Crocin on BRL-3A in the environment of H2O2. Results. SWGNS reversed weight loss is induced by CCl4. Serum assays showed that SWGNS reduced CCl4-induced alanine aminotransferase, aspartate aminotransferase, total bilirubin, and γ-glutamyltransferase levels and increased the total protein and albumin levels. Histopathological evaluation showed that SWGNS alleviated hepatic steatosis, fibrosis, and inflammation. Furthermore, SWNGS reduced CCl4-induced elevations of TGF-β1, hyaluronic acid, laminin, and collagen IV in serum and reduced the high expression of α-SMA in tissues. Moreover, Crocin I and II are the main components of SWGNS. Crocin attenuated the damaging effects of H2O2 on BRL-3A. Conclusions. In conclusion, SWGNS alleviated CCl4-induced chronic liver injury by inhibiting the TGF-β1 pathway. This plays an important role in promoting traditional Tibetan medicine in clinical practice.

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Thymosin β4 suppresses CCl₄‐induced murine hepatic fibrosis by down‐regulating transforming growth factor β receptor‐II

Abstract: Tβ4 possesses anti-fibrotic activity in the liver, which is attributable, at least partly, to down-regulating TGF-βRII and thereby blunting TGF-β1-mediated fibrogenetic signaling in both HSCs and hepatocytes.

Cited by 12 publications

References 44 publications

Thymosin Beta 4 Improves the Intestinal Ischemia/Reperfusion Injury in Rats

Thymosin Beta 4 Improves the Intestinal Ischemia/Reperfusion Injury in Rats

Single-cell proteomics reveals changes in expression during hair-cell development

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-β1 in Wistar Rats

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Thymosin β4 suppresses CCl4‐induced murine hepatic fibrosis by down‐regulating transforming growth factor β receptor‐II

Abstract: Tβ4 possesses anti-fibrotic activity in the liver, which is attributable, at least partly, to down-regulating TGF-βRII and thereby blunting TGF-β1-mediated fibrogenetic signaling in both HSCs and hepatocytes.

Cited by 12 publications

References 44 publications

Thymosin Beta 4 Improves the Intestinal Ischemia/Reperfusion Injury in Rats

Thymosin Beta 4 Improves the Intestinal Ischemia/Reperfusion Injury in Rats

Single-cell proteomics reveals changes in expression during hair-cell development

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-β1 in Wistar Rats

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Thymosin β4 suppresses CCl₄‐induced murine hepatic fibrosis by down‐regulating transforming growth factor β receptor‐II