OBJECTIVEOvarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis.

DATA SOURCESWe searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms.

STUDY SELECTIONArticles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases.

RESULTSMany cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide.

CONCLUSIONSPatients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

Animals ; Cytokines ; metabolism ; Female ; Fibrosis ; complications ; diagnosis ; etiology ; metabolism ; Humans ; Infertility, Female ; etiology ; Ovary ; pathology

miRNAs are important post-transcriptional regulators. The aberrant expression of miRNAs is strongly associated with the initiation and progression of pathophysiologic processes in a wide range of human diseases. Scleroderma (systemic sclerosis; SSc) is a highly heterogeneous autoimmune disease that includes the progressive fibrotic replacement of normal tissue architecture in multiple organs. Our previous studies have suggested that SSc skin tissues display a different miRNA expression signature than that found in normal controls. miRNAs with pro- or antifibrotic properties are found to be dysregulated in SSc skin fibrosis. Serum miRNA levels are associated with SSc activity and severity. miRNAs have the potential to be therapeutic targets and serve as biomarkers for SSc diagnosis and assessment of disease state and severity. This review summarizes the SSc miRNA expression signature and the roles of dysregulation of miRNAs in SSc tissues and serum and examines the future therapeutic potential of targeting miRNAs in the management of SSc patients.
Animals ; Biological Markers/metabolism ; Fibrosis/etiology/metabolism ; Humans ; MicroRNAs/*genetics/metabolism ; Scleroderma, Systemic/diagnosis/etiology/genetics/*metabolism

No abstract available.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism

In acute injury, liver recovers completely without any scarring change or complication. However, large portion of liver is changed into fibrotic state by excessive production of extracellular matrix (ECM) under chronic injury. Excessive production of ECM results in hepatic fibrosis and repeated process of hepatic fibrosis progress into liver cirrhosis. Liver cirrhosis is an irreversible and terminal state of chronic liver disease and one of the major causes of death in Korea. To block the progression to liver cirrhosis, various studies in the field of virology and immunology have been proceeded. Recently, studies on the hepatic fibrogenesis have progressed with the development of molecular biology. Hepatic stellate cells (HSC) play a key role in the pathogenesis of hepatic fibrosis by producing ECM. The degree of hepatic fibrosis depends on the proliferation and activation of HSC and increased net production of collagen. Therefore, inhibition of HSC activation is one of the main ways to block the progression of hepatic fibrosis. Many kinds of factors such as oxidative stress, acetaldehyde, ascorbic acid, transforming growth factor-beta (TGF-beta) and carbon tetrachloride (CCl4) have been reported to activate HSC and stimulate collagen gene expression. Although there are no definite and effective antifibrogenic agents, possible candidates are antioxidants, interferon, retinoids such as beta-carotene, flavonoids, renin-angiotensin system inhibitors and peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists. We tried to evaluate the charateristics of HSC in order to develop agents that inhibit hepatic fibrogenesis.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism

OBJECTIVETo study the impact of pulmonary fibrosis on erectile function in rats and its mechanism.

METHODSForty 12-week-old healthy male SD rats were randomly divided into Groups A (4-week pulmonary fibrosis), B (6-week pulmonary fibrosis), C (4-week control, and D (6-week control). The models of pulmonary fibrosis were established by injection of bleomycin at 5 mg/kg in the trachea, while the controls were injected with normal saline only. At 4 and 6 weeks, all the rats were subjected to determination of the serum testosterone (T) level, arterial blood gas analysis, measurement of intracavernous pressure/mean arterial pressure (ICP/MAP), and examination of NOS activity and cGMP content. The mRNA expressions of eNOS, iNOS and nNOS in the corpus cavernosum penis were detected by real-time PCR, and that of eNOS analyzed by Western blot.

RESULTSThe 3 V and 5 V of the ICP/mapx100 in Group C were 16.37 +/- 2.19 and 27.19 +/- 3.18, significantly lower than 30.78 +/- 2.66 and 50.09 +/- 6.97 in Group A (P < 0.05); those in Group D were 10.17 +/- 1.31 and 17.40 +/- 1.74, significantly lower than 31.45 +/- 3.07 and 51.23 +/- 7.23 in Group B (P < 0.05), and so were they in Group D than in C (P < 0.05). PaO2 was significantly lower in Group C than in A ([75.50 +/- 13.87] mmHg vs [103.80 +/- 6.88] mmHg, P < 0.05) , and so was it in Group D than in B ( [83.60 +/- 5.50] mmHg vs [102.70 +/- 5.77] mmHg, P < 0.05). Group C showed a significantly increased serum T level as compared with A ([391.1 +/- 264.7] ng/dl vs [175.9 +/- 53.0] ng/dl, P < 0.05), so did Group D ([745.4 +/- 408.8] ng/dl) versus Group B ([177.8 +/- 52.3] ng/dl) and C (P < 0.05). NOS activity and cGMP content in the corpus cavernosum significantly decreased in Group C ([1.50 +/- 0.14] U/mg prot and [35.69 +/- 3.64] pmol/mg) compared with A ([2.66 +/- 0.39] U/mg prot and [51.10 +/- 7.22] pmol/mg) (P < 0.05), so did they in D ([1.40 +/- 0.20] U/mg prot and [34.55 +/- 4.30] pmol/mg) versus B ([2.75 +/- 0.36] U/mg prot and [52.15 +/- 6.86] pmol/mg) (P < 0.05), but neither showed any significant difference between Groups D and C (P > 0.05). The expression of the eNOS protein was significantly lower in Group C than in A (0.79 +/- 0.01 vs 0.87 +/- 0.01, P < 0.05), so was it in D than in B and C (0.71 +/- 0.02 vs 0.88 +/- 0.01 and 0.79 +/- 0.01, P < 0.05). The expression of eNOS mRNA was significantly higher in Group C than in A (4.46 +/- 0.92 vs 2.61 +/- 0.68, P < 0.05), but did not show any significant difference between D and B (2.79 +/- 0.60 vs 2.69 +/- 0.65, P > 0.05), nor did the expressions of nNOS mRNA and iNOS mRNA between the pulmonary fibrosis groups and the controls (P > 0.05).

CONCLUSIONPulmonary fibrosis may induce erectile dysfunction by suppressing the expression of the eNOS protein and reducing NOS activity and cGMP content in the corpus cavernosum penis of rats.

Animals ; Erectile Dysfunction ; etiology ; metabolism ; Male ; Nitric Oxide Synthase ; metabolism ; Penis ; metabolism ; Pulmonary Fibrosis ; complications ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases. DATA SOURCES: This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases." STUDY SELECTION: Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English. RESULTS: SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome. CONCLUSIONS Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.
Acute Kidney Injury ; etiology ; Carcinoma, Renal Cell ; etiology ; Diabetic Nephropathies ; etiology ; Fibrosis ; Humans ; Kidney ; pathology ; Kidney Diseases ; etiology ; metabolism ; Kidney Neoplasms ; etiology ; SUMO-1 Protein ; physiology ; Sumoylation

Humans ; Interleukin-18 ; chemistry ; metabolism ; Pulmonary Fibrosis ; etiology ; pathology ; Silicosis ; complications ; pathology ; physiopathology

The hallmark of scleroderma is fibrosis by excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs. Increasing evidence suggests that overexpression of transforming growth factor-beta (TGF-beta) and its receptors play a key pathogenic role in the development of tissue fibrosis in scleroderma. TGF-beta is known to induce the expression of ECM proteins in the pathogenesis of fibrosis in systemic sclerosis. Investigations into TGF-beta pathways will suggest new treatment strategies for fibrotic diseases.
Animals ; Extracellular Matrix ; metabolism ; pathology ; Extracellular Matrix Proteins ; metabolism ; Fibroblasts ; metabolism ; Fibrosis ; Humans ; Receptors, Transforming Growth Factor beta ; metabolism ; Scleroderma, Systemic ; etiology ; metabolism ; Transforming Growth Factor beta ; metabolism

The aim of this article was to investigate the mechanisms of emodin in antagonizing against organ fibrosis, and to illustrate that emodin can be an effective Chinese herbal preparation for treatment of organ fibrosis.
Animals ; Emodin ; therapeutic use ; Fibrosis ; drug therapy ; Glomerulosclerosis, Focal Segmental ; drug therapy ; etiology ; Humans ; Kidney ; metabolism ; pathology ; Liver Cirrhosis ; drug therapy ; Phytotherapy ; Pulmonary Fibrosis ; drug therapy

OBJECTIVEThe aim of this study was to explore the diagnostic value of liver stiffness measurement combined with serum high-sensitivity C-reactive protein detection in HBV-related cirrhosis patients complicated with primary liver cancer.

METHODSA total of 156 previously untreated chronic hepatitis B-related cirrhosis patients and 50 healthy subjects were included in this study. The 156 patients were divided into two groups: those with primary liver cancer (67 cases) and without liver cancer (89 cases). The 50 healthy subjects were considered as normal control group. Liver stiffness measurement (LSM) was conducted and serum high-sensitivity C-reactive protein (CRP) level was assayed in all the 156 patients and 50 normal individuals, and their measurement values were statistically compared and analyzed.

RESULTSThe LSM value was (39.72±29.05) kPa in the liver cancer patients, significantly higher than the (27.81±18.46) kPa in the cirrhosis alone patients and (4.25±0.74) kPa in the healthy controls (P<0.01 for both). Serum hs-CRP levels in the liver cancer patients was 5.81mg/L, significantly higher than 1.78 mg/L in the cirrhosis alone patients and 0.38mg/L in healthy controls, (P<0.01 for both). The higher the grade of LSM values was, the positive rate of CRP was higher in the cirrhosis patients complicated with primary liver cancer. In patients with LSM values ≥27.6 kPa, the serum CRP positive rate was 64.2% in patients with primary liver cancer, significantly higher than the 38.0% in patients with cirrhosis alone (P<0.01). In the 67 HBV-related cirrhosis patients complicated primary liver cancer, the LSM value and serum hs-CRP level in AFP-positive patients were (48.95±28.59) kPa and 4.91 mg/L, respectively, higher than those in the AFP-negative patients (28.64±26.83) kPa and 4.16 mg/L, but with a non-significant difference (P>0.05).

CONCLUSIONLiver stiffness measurement combined with serum high-sensitivity C-reactive protein detection may have potential diagnostic implications as a marker of primary liver cancer occurrence in patients with HBV-related cirrhosis.

Biomarkers ; C-Reactive Protein ; metabolism ; Elasticity Imaging Techniques ; Fibrosis ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; metabolism ; virology ; Liver Neoplasms