The antifibrotic effects of TGF-β1 siRNA on hepatic fibrosis in rats

Lang, Qing; Liu, Qi; Xu, Ning; Qian, Keli; Qi, Jing-hu; Sun, Yao; Xiao, Lei; Shi, Xiaofeng

doi:10.1016/j.bbrc.2011.05.023

Cited by 53 publications

(19 citation statements)

References 24 publications

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“…Androgen deficiency induces bladder fibrosis and decreases the bladder maximal volume and compliance which could be effectively prevented by TRT (Gallo et al 2012;Zhang et al 2012;de Barros et al 2013). The expression of TGF-beta, a common profibrotic factor, is upregulated by androgen deficiency, which induces procollagen production and consequently UB fibrosis and dysfunction (Matsuoka and Tsukamoto 1990;Wen et al 2010;Lang et al 2011;Samarakoon et al 2012).…”

Section: Discussionmentioning

confidence: 98%

Effect of testosterone therapy on the urinary bladder in experimental hypogonadism of rats

Abdel-Hamid

Ali

2015

J Mol Hist

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Testosterone (T) deficiency is prevalent particularly in elderly men and lead to physical and sexual morbidities. Although low levels of T are associated with low urinary tract symptoms, the correlation between T deficiency and bladder dysfunction is not clearly identified. The aim of this study was to investigate the effect of high dose testosterone replacement therapy (TRT) on the histological structure of the UB in castrated rats. Twenty-five adult male rats were divided into three groups: control, castrated and castrated + TRT. T was administrated in high dose (100 mg/kg) two intramuscular injections/week for 60 days. UB sections were prepared and stained with H&E, Masson's trichrome and immunohistochemical detection of Cytokeratin 20 (Ck20). All data were morphometrically and statistically analyzed. In castrated group, significant atrophy of the urothelium (P < 0.001) accompanied with widening of the corium were observed. The smooth muscle appeared thin with marked increase in the collagen fibers. On treating the castrated group with TRT, atypical Ck20 expression as well as significant increase in urothelial thickness (P < 0.05) and smooth muscle/collagen ratio (P < 0.001) were detected. In castrated rat model, high dose TRT has a positive effect on the UB smooth muscle rather than the urothelium which acquired atypical patterns.

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Section: Discussionmentioning

confidence: 98%

Effect of testosterone therapy on the urinary bladder in experimental hypogonadism of rats

Abdel-Hamid

Ali

2015

J Mol Hist

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“…In the liver, the TGF-β family contains three closely related isoforms (i.e., TGF-β1, TGF-β2, and TGF-β3), which have similar biological activities in liver fibrosis [37]. TGF-β1, as the main profibrogenic mediator, mainly activates HSC and causes liver fibrosis through TGF-β1/Smad signal pathway [35,38]. Many studies showed that TGF-β2 can induce fibrotic marker expression and play a vital role in the fibrotic diseases [39].…”

Section: Discussionmentioning

confidence: 99%

The Epigenetically-Regulated microRNA-378a Targets TGF-β2 in TGF-β1-Treated Hepatic Stellate Cells

Yang

Huang³

et al. 2016

Cell Physiol Biochem

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Background/Aims: In liver fibrosis, the activation of hepatic stellate cells (HSCs) is considered as a pivotal event. It is well known that transforming growth factor-β1 (TGF-β1) is the main stimuli factor responsible for HSC activation. microRNAs (miRNAs), regulating various biological processes, have recently been shown to be involved in HSC activation. A recent study reported that deficiency of miR-378a contributes to cardiac fibrosis via TGF-β1-dependent paracrine mechanism. However, the involvement of miR-378a and its roles in TGF-β1-induced HSC activation remains largely unknown. Methods: miR-378a expression was detected in TGF-β1-treated cells and patients with cirrhosis. Then, effects of miR-378a overexpression on cell proliferation and HSC activation were analyzed. We also analyzed the binding of miR-378a to the 3′-untranslated region of TGF-β2. Results: In response to TGF-β1, miR-378a expression was down-regulated in a dose-dependent manner. miR-378a overexpression suppressed both cell proliferation and cell cycle in TGF-β1-treated LX-2 cells. Moreover, miR-378a overexpression inhibited TGF-β1-induced HSC activation including the reduction of α-smooth muscle actin (α-SMA) and type I collagen. Similarly, miR-378a resulted in a reduction in cell proliferation, and the expressions of α-SMA and Col1A1 in TGF-β1-treated primary HSCs. Notably, TGF-β2 was confirmed as a target of miR-378a by luciferase reporter assays. Interestingly, miR-378a promoter methylation may be responsible for miR-378a down-regulation in TGF-β1-treated LX-2 cells and TGF-β1-treated primary HSCs. Further studies confirmed that reduced miR-378a was associated with promoter methylation in patients with cirrhosis compared with healthy controls. Conclusion: Our results demonstrate that miR-378a expression is associated with its methylation status in TGF-β1-treated cells, and epigenetically-regulated miR-378a inhibits TGF-β1-induced HSC activation, at least in part, via TGF-β2.

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“…TGF-β 1 is a common profibrotic factor that mediates the pathologic process of fibrosis in multiple organs (Matsuoka and Tsukamoto 1990;Wen et al 2010;Lang et al 2011;Samarakoon et al 2012). Matsuoka and Tsukamoto (1990) found that TGF-β 1 plays critical role in pathogenetic role in alcoholic liver fibrogenesis by stimulation of hepatic lipocyte collagen production.…”

Section: Discussionmentioning

confidence: 99%

“…However the intermediate molecule and signaling pathway are unknown. Realizing that TGF-β 1 is a common profibrotic factor which mediates the pathologic process of fibrosis in multiple organs (Matsuoka and Tsukamoto 1990;Wen et al 2010;Lang et al 2011;Samarakoon et al 2012), we hypothesize that TGF-β 1 is responsible for androgen deprivation-induced fibrosis in bladder tissues. To test this hypothesis, firstly we measured the TGF-β 1 mRNA levels Androgen deprivation induced TGF-β production contributes to induction of pro-collagen I mRNA expression level.…”

Section: Tgf-β Is a Signaling Molecule Responsible For Androgen Deprimentioning

confidence: 98%

Androgen Deprivation Induces Bladder Histological Abnormalities and Dysfunction via TGF-.BETA. in Orchiectomized Mature Rats

Zhang

Ji-min

et al. 2012

Tohoku J. Exp. Med.

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Symptomatic late-onset hypogonadism, one of the most common elder diseases, is defined as a syndrome associated with a deficiency in serum testosterone. Recent studies have indicated that androgen deficiency in men is also associated with lower urinary tract symptoms and bladder dysfunction. To determine the pathologic consequences of androgen deprivation in bladder histology and function, we addressed the underlying mechanism. Male rats were divided into 4 groups: emasculated rats (EMR), emasculated rats treated with testosterone, emasculated rats treated with anti-transforming growth factor-β (TGF-β) neutralizing antibody, and sham surgery rats. TGF-β is a common profibrotic factor that mediates the pathologic process of fibrosis in multiple organs. Two months later, urodynamic evaluations were employed to determine the bladder function in vivo. And then rats were sacrificed, and the bladder tissues were collected. Histological studies were employed to determine the degree of bladder fibrosis. Real time PCR was used to evaluate the mRNA level of pro-collagen I, a fibrotic marker. We demonstrate here that androgen deficiency induces bladder fibrosis and decreases the bladder maximal volume and compliance. Androgen replacement treatment completely prevented the histological and functional abnormalities induced by androgen deficiency. Subsequently, we identified that androgen deprivation induced the induction of TGF-β mRNA level. Importantly, treatment with anti-TGF-β antibody abolished androgen deprivation-induced bladder fibrosis and dysfunction. Our study reveals an essential role of TGF-β in the pathogenesis of androgen deprivation-induced bladder fibrosis and dysfunction and offers a potential target for prevention and treatment of bladder dysfunction associated with androgen deficiency.

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The antifibrotic effects of TGF-β1 siRNA on hepatic fibrosis in rats

Cited by 53 publications

References 24 publications

Effect of testosterone therapy on the urinary bladder in experimental hypogonadism of rats

Effect of testosterone therapy on the urinary bladder in experimental hypogonadism of rats

The Epigenetically-Regulated microRNA-378a Targets TGF-β2 in TGF-β1-Treated Hepatic Stellate Cells

Androgen Deprivation Induces Bladder Histological Abnormalities and Dysfunction via TGF-.BETA. in Orchiectomized Mature Rats

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