• Journal of Korean Biological Nursing Science
• /
• v.8 no.2
• /
• pp.41-59
• /
• 2006

Chronic liver diseases and hepatic cancer have been reported as 10% of cause of death in Koreans. Regardless of various causes, chronic liver disease accompanies commonly hepatic fibrosis. But still the mechanism of hepatic fibrosis remains poorly understood. Using the dimethylnitrosamine(DMN)-induced hepatic fibrosis rat model, We performed to evaluate the possible therapeutic effect of RIP(extracts of Phellodendron amurense and Patrinia scabiosaefolia) and to investigate the changes in referential connective tissue proteins($TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin, and vimentin) as a marker of fibrogenesis. For these purposes, liver tissues were stained with H & E, and Azan staining for estimation of developing fibrosis. In the DMN-treated rat liver tissue, fibrosis were developed forming incomplete septal fibrosis. Whereas, in the RIP-treated rat liver tissues, the fibrosis were decreased recovering to normal morphology. The expressions of $TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin($\alpha-SMA$), and vimetin were increased in the DMN-treated rat liver tissues, but decreased in the various areas of RIP-treated rat liver tissues. According to these results, RIP could be a possible therapeutic agent to reduce hepatic fibrosis, and the $TGF-{\beta}_1$, ${\alpha}$-SMA, and vimentin could be possible indicative markers of hepatic fibrosis development and recovery.

• Biomolecules & Therapeutics
• /
• v.30 no.2
• /
• pp.126-136
• /
• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• Clinical and Experimental Pediatrics
• /
• v.53 no.7
• /
• pp.735-740
• /
• 2010

Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

• Biomolecules & Therapeutics
• /
• v.27 no.3
• /
• pp.318-326
• /
• 2019

Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 ($S1P_2$) has not been fully investigated. Therefore, in this study, the roles of $S1P_2$ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the $7^{th}$ day after bleomycin administration, $S1P_2$ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the $28^{th}$ day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from $S1P_2$ deficient mice showed less inflammation and fibrosis. Increase in TGF-${\beta}1$-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a $S1P_2$ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of $S1P_2$ were elucidated using a bleomycin-induced fibrosis model. Notably, $S1P_2$ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that $S1P_2$ could be a promising therapeutic target for the treatment of pulmonary fibrosis.

• Journal of Yeungnam Medical Science
• /
• v.37 no.4
• /
• pp.269-276
• /
• 2020

Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

• Tuberculosis and Respiratory Diseases
• /
• v.85 no.4
• /
• pp.320-331
• /
• 2022

Coronavirus disease 2019 (COVID-19) has become a major health burden worldwide, with over 450 million confirmed cases and 6 million deaths. Although the acute phase of COVID-19 management has been established, there is still a long way to go to evaluate the long-term clinical course or manage complications due to the relatively short outbreak of the virus. Pulmonary fibrosis is one of the most common respiratory complications associated with COVID-19. Scarring throughout the lungs after viral or bacterial pulmonary infection have been commonly observed, but the prevalence of post-COVID-19 pulmonary fibrosis is rapidly increasing. However, there is limited information available about post-COVID-19 pulmonary fibrosis, and there is also a lack of consensus on what condition should be defined as post-COVID-19 pulmonary fibrosis. During a relatively short follow-up period of approximately 1 year, lesions considered related to pulmonary fibrosis often showed gradual improvement; therefore, it is questionable at what time point fibrosis should be evaluated. In this review, we investigated the epidemiology, risk factors, pathogenesis, and management of post-COVID-19 pulmonary fibrosis.

• Journal of the Korean Society of Radiology
• /
• v.13 no.4
• /
• pp.539-546
• /
• 2019

Liver biopsy is invasive and it is a risk of complications. Nevertheless, liver biopsy is gold standard for predicting liver fibrosis. To compensate for these shortcomings, in this study, the liver fibrosis stage was divided using Fibroscan(R) in 200 chronic hepatitis C patients. And, the usefulness and cut-off values of fibrosis index based on four factors(FIB-4), AST to platelet ratio index(APRI) and AST/ALT ratio(AAR) calculated as serum tests were investigated by analyzing ROC curve. As a result, using FIB-4 and APRI rather than AAR is appropriate for evaluation of liver fibrosis. And using APRI to predict significant Fibrosis(F2) and FIB-4 is considered useful for predicting cirrhosis(F4). By applying the advantages of the serum based liver fibrosis marker, which are convenient and repeatable, liver fibrosis follow-up term can be reduced, and furthermore, the prevalence of liver cirrhosis and hepatocellular carcinoma(HCC) can be reduced.

• The Korea Journal of Herbology
• /
• v.37 no.6
• /
• pp.9-17
• /
• 2022

Objective : In modern society, liver diseases such as liver fibrosis are on the rise as inflammation and wound healing processes of the liver are repeated due to factors such as drinking, smoking, and stress. This study was conducted to evaluate the effect of Saenggangeonbi-tang (SGGBT) on thioacetamide (TAA)-induced liver fibrosis. Methods : The mice were divided into 4 groups for examination (n=6): Normal group (Nor), distilled water-treated liver fibrosis mice (Con), silymarin 50 mg/kg-treated liver fibrosis mice (Sily), SGGBT 200 mg/kg-treated liver fibrosis mice (S200). Liver fibrosis was established in the mice via TAA for 8 weeks (1 week 100 mg/kg, 2,3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg, three times a week, intraperitoneal injection) and they were administered silymarin and SGGBT (every day, oral administration) with the TAA. Results : SGGBT significantly decreased the levels of aspartate aminotransferase, alanine aminotransferanse, ammonia, and myeloperoxidase in serum increased by liver fibrosis. As a result of confirming H&E and MT staining, it was confirmed that SGGBT reduced damage and inflammatory cell infiltration in liver tissue, and alleviated changes in collagen fiber deposition and histological fibrosis. Also, it was confirmed through PAS staining that it reduced glycogen deposition in liver tissue. In addition, SGGBT significantly decreased the NADPH oxidases as well as significantly modulated the expression of MMP-2 and TIMP-2. Conclusions : These results suggest that SGGBT regulates the expression of MMP/TIMP protein through inhibition of oxidative stress and alleviates liver fibrosis by reducing collagen and glycogen deposition in liver tissue.

• The Journal of Pediatrics of Korean Medicine
• /
• v.23 no.3
• /
• pp.233-240
• /
• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. Weperformed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• Clinical and Experimental Pediatrics
• /
• v.56 no.2
• /
• pp.45-51
• /
• 2013

Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.