Inhibition of Janus kinase-2 signalling pathway ameliorates portal hypertensive syndrome in partial portal hypertensive and liver cirrhosis rats

Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis

“…Phosphorylated JAK2 activates the nucleotide exchange factor for RHOA, ARHGEF1, which then activates the RHOA cascade towards ROCK in HSCs 10 11. Thus, there are several lines of evidence that stimulation of this pathway via the AT1R leads to activation of HSCs and thereby increased fibrosis, while the inhibition of JAK2 is antifibrotic,10 which has recently been confirmed by others 18. The present study assessed the close association of the hepatic RAS pathway—known to be a driver of complications,4 29 30 more specifically ACE and AT1R —with the transcription of the JAK2/ROCK pathway components in the human liver cirrhosis.…”

“…The Jak2 deficiency in these cells was associated with a less activated RHOA/ROCK pathway and these animals showed less hepatic fibrogenesis with lower PP in two different models of liver fibrosis. The lower PP in the conditional knock-out model of Jak2 —or following chronic pharmacological JAK2 inhibition18—is not surprising since these animals showed less advanced fibrosis, which is associated with a lower PP through reduction in the ‘fixed’, ‘passive’ part of increased intrahepatic vascular resistance. To circumvent this latter factor, we studied the haemodynamic effect of acute pharmacological JAK2 inhibition by use of microspheres.…”

“…While the long-term treatment with JAK2 inhibitors decreases experimental fibrosis,10 18 the acute effect of JAK2 inhibition on portal pressure (PP) remains unknown. Acute modulation of PP is of important clinical relevance.…”

Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension

“…Compared with the PIH group, we observed that the AG490 group had lower SBP and UP levels. Wang and his colleagues reported that AG490 ameliorated portal hypertensive syndrome in partial portal hypertensive and liver cirrhosis rats via inhibition of JAK2/STAT3 signaling as well as its downstream cytokines [22]. Additionally, AG490 treatment can significantly improve renal function, reduce proteinuria and suppress histological lesions of the kidneys and salivary glands in lupus nephritis rats [23].…”

The Importance of Strains in Choose of Laboratory Animal Models: Review

“…Bu nedenlerle her çalışma için uygun türün saptanması gerektiği gibi, en uygun olan soyun da belirlenmesinin çalışmanın en doğru şekilde tasarımı, gerçeğe en yakın modelin oluşturulabil-mesi ve istenen sonuca en yakın doğrulukta verilerle ulaşılabilmesi açısından önemli olduğu görülmektedir. [11][12][13][14] Hayvan modelleri oluşturulur iken, biyoteknoloji biliminin sunduğu olanaklarla genel anlamda birçok modele uygun hayvan soylarının yanında, çok daha spesifik çalışmalar için genetik yönden tanımlanmış özel soyları üretmek de mümkün olmaktadır.…”