Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord–Derived Mesenchymal Stem Cells

BACKGROUND AND OBJECTIVES: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). METHODS AND RESULTS: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. CONCLUSIONS: H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs.

Spectrum of Novel Hereditary Hemorrhagic Telangiectasia Variants in an Austrian Patient Cohort

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disorder characterized by pathogenic blood vessel development and maintenance. HHT type 1 (HHT1) and type 2 (HHT2) are caused by variants in endoglin (ENG) and activin receptor-like kinase-1 (ACVRL1), respectively. The aim of this study was to identify the spectrum of pathogenic variants in ENG and ACVRL1 in Austrian HHT families. METHODS: In this prospective study, eight Austrian HHT families were screened for variants in ENG and ACVRL1 by polymerase chain reaction amplification and sequencing of DNA isolated from peripheral blood. RESULTS: Heterozygous variants were identified in all families under study. HHT1 was caused by a novel c.816+1G>A splice donor variant, a novel c.1479C>A nonsense (p.Cys493X) variant and a published c.1306C>T nonsense (p.Gln436X) variant in ENG. Variants found in ACVRL1 were novel c.200G>C (p.Arg67Pro) and known c.772G>A (p.Gly258Ser) missense variants in highly conserved residues, a known heterozygous c.100dupT frameshift (p.Cys34Leufs*4) and the known c.1204G>A missense (p.Gly402Ser) and c.1435C>T nonsense (p.Arg479X) variants as causes of HHT2. CONCLUSION: Novel and published variants in ENG (37.5%) and ACVRL1 (62.5%) were exclusively identified as the cause of HHT in an Austrian patient cohort. Identification of novel causative genetics variants should facilitate the development of tailored therapeutical applications in the future treatment of autosomal dominant HHT.

Elevated serum Activin A in chronic obstructive pulmonary disease with skeletal muscle wasting

OBJECTIVE: Muscle wasting contributes to the reduced quality of life and increased mortality in chronic obstructive pulmonary disease (COPD). Muscle atrophy in mice with cachexia was caused by Activin A binding to ActRIIB. The role of circulating Activin A leading to muscle atrophy in COPD remains elusive. METHODS: In the present study, we evaluated the relationship between serum levels of Activin A and skeletal muscle wasting in COPD patients. The expression levels of serum Activin A were measured in 78 stable COPD patients and in 60 healthy controls via ELISA, which was also used to determine the expression of circulating TNF-α levels. Total skeletal muscle mass (SMM) was calculated according to a validated formula by age and anthropometric measurements. The fat-free mass index (FFMI) was determined as the fat-free mass (FFM) corrected for body surface area. RESULTS: Compared to the healthy controls, COPD patients had upregulated Activin A expression. The elevated levels of Activin A were correlated with TNF-α expression, while total SMM and FFMI were significantly decreased in COPD patients. Furthermore, serum Activin A expression in COPD patients was negatively associated with both FFMI and BMI. CONCLUSION: The above results showed an association between increased circulating Activin A in COPD patients and the presence of muscle atrophy. Given our previous knowledge, we speculate that Activin A contributes to skeletal muscle wasting in COPD.

TGF-β induces Smad2 Phosphorylation, ARE Induction, and Trophoblast Differentiation

BACKGROUND: Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated. MATERIALS AND METHODS: In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF-β induced differentiation. Activation of the TGF-β pathway and the ability of TGF-β to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis. RESULTS AND CONCLUSIONS: In this report, we show that three isoforms of TGF-β have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF-β superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF-β induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.

Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2

OBJECTIVE: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model. METHODS: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.0 μg, 6.0 μg, or 10.0 μg of rhBMP2 with osteon; and 1.0 μg, 3.0 μg, 6.0 μg, or 10.0 μg of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry. RESULTS: Bone fusion scores were significantly higher for 10.0 μg AB204 and 10.0 μg rhBMP2 than for osteon only or 1.0 μg AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and 10.0 μg, but, the properties of AB204 at doses of 3.0 μg exhibited better than the properties of rhBMP2 at doses of 3.0 μg. CONCLUSION: AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

In vitro differentiation of spermatogonial stem cells using testicular cells from Guangxi Bama mini-pig

In this study, we attempted to establish a culture system for in vitro spermatogenesis from spermatogonial stem cells (SSCs) of Bama mini-pig. Dissociated testicular cells from 1-month-old pigs were co-cultured to mimic in vivo spermatogenesis. The testicular cells were seeded in minimum essential medium alpha (α-MEM) supplemented with Knockout serum replacement (KSR). Three-dimensional colonies formed after 10 days of culture. The colonies showed positive staining for SSC-associated markers such as UCHL1, PLZF, THY1, OCT4, Dolichos biflorus agglutinin, and alkaline phosphatase. Induction of SSCs was performed in α-MEM + KSR supplemented with retinoic acid, bone morphogenetic protein 4, activin A, follicle-stimulating hormone, or testosterone. The results showed that STRA8, DMC1, PRM1, and TNP1 were upregulated significantly in the colonies after induction compared to that in testis from 1-month-old pigs, while expression levels of those genes were significantly low compared to those in 2-month-old testis. However, upregulation of ACROSIN was not significant. Replacement of α-MEM and KSR with Iscove's modified Dulbecco's medium and fetal bovine serum did not upregulate expression of these genes significantly. These results indicate that SSCs of Bama mini-pig could undergo differentiation and develop to a post-meiotic stage in α-MEM supplemented with KSR and induction factors.

Interactive Roles of Activin A in Epidermal Regeneration

No abstract available.

Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2

OBJECTIVE: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model.METHODS: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.0 μg, 6.0 μg, or 10.0 μg of rhBMP2 with osteon; and 1.0 μg, 3.0 μg, 6.0 μg, or 10.0 μg of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry.RESULTS: Bone fusion scores were significantly higher for 10.0 μg AB204 and 10.0 μg rhBMP2 than for osteon only or 1.0 μg AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and 10.0 μg, but, the properties of AB204 at doses of 3.0 μg exhibited better than the properties of rhBMP2 at doses of 3.0 μg.CONCLUSION: AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

Recent Topics in Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease that is characterized by the formation of heterotopic bone tissues in soft tissues, such as skeletal muscle, ligament, and tendon. It is difficult to remove such heterotopic bones via internal medicine or invasive procedures. The identification of activin A receptor, type I (ACVR1)/ALK2 gene mutations associated with FOP has allowed the genetic diagnosis of FOP. The ACVR1/ALK2 gene encodes the ALK2 protein, which is a transmembrane kinase receptor in the transforming growth factor-β family. The relevant mutations activate intracellular signaling in vitro and induce heterotopic bone formation in vivo. Activin A is a potential ligand that activates mutant ALK2 but not wild-type ALK2. Various types of small chemical and biological inhibitors of ALK2 signaling have been developed to establish treatments for FOP. Some of these are in clinical trials in patients with FOP.

Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.

Biochemical and genetic studies on inhibin as a hormonal candidate in prediction and diagnosis of premature ovarian failure in the Egyptian women

Background: Recent studies have implicated a role for inhibin alpha [INH alpha] gene abnormalities in the etiology of premature ovarian failure [POF].The present study aimed at demonstrating the possibility that -16C>T polymorphism of INH alpha gene may enhance susceptibility to this disease among Egyptian women undergoingt in-vitro fertilization[IVF] technique

Methods: A total of 50 POF Egyptian women at age [31.5 +/- 7.3] and 50 control women at age [29.1 +/- 6.8] were included in this study. Genotyping of INH alpha-16C>T gene was performed by restriction fragment length polymorphism. Levels of inhibin, activin, FSH and LH were also assessed

Results: Serum levels of FSH and LH showed significant increase coupled by decrease in serum inhibin and inhibin/activin ratio, however, levels of activin were within normal values in POF women comparing to control ones. The frequencies of CC, CT and TT genotypes showed no significant changes in POF women compared to control group. Moreover, there were no significant differences in frequency of C and T alleles among the POF women in comparison to controls

Conclusion: Obtained data indicated that -16C>T polymorphism of INH alpha gene can not imply a functional effect on the current decline of serum inhibin and hence the risk of developing POF in the studied Egyptian women. Further studies on POF women are needed to expand the present data

Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

Follistatin N terminus differentially regulates muscle size and fat in vivo

Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV). Overexpression of wild-type FST in normal mice greatly increased muscle mass while decreasing fat accumulation, whereas overexpression of an N terminus mutant or N terminus-deleted FST had no effect on muscle mass but moderately decreased fat mass. In contrast, FST-I-I containing the complete N terminus and double domain I without domain II and III had no effect on fat but increased skeletal muscle mass. The effects of different constructs on differentiated C2C12 myotubes were consistent with the in vivo finding. We hypothesized that ND was critical for myostatin blockade, mediating the increase in muscle mass, and was less pivotal for activin binding, which accounts for the decrease in the fat tissue. An in vitro TGF-beta1-responsive reporter assay revealed that FST-I-I and N terminus-mutated or -deleted FST showed differential responses to blockade of activin and myostatin. Our study provided direct in vivo evidence for a role of the ND of FST, shedding light on future potential molecular designs for FST-based gene therapy.

C-terminal-truncated HBV X promotes hepato-oncogenesis through inhibition of tumor-suppressive β-catenin/BAMBI signaling

C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein. Ectopic ctHBx expression generated more colonies in anchorage-dependent and -independent growth assays than did HBx expression alone. ctHBx downregulated BAMBI to a greater degree than did HBx in HCC cells. HBx activated the Wnt/β-catenin pathway, which positively regulated the BAMBI expression through T-cell factor 1 signaling, whereas ctHBx negatively regulated the Wnt/β-catenin pathway. BAMBI downregulated the β-catenin and TGF-β1 signaling pathways. TGF-β1 positively regulated BAMBI expression thorough Smad3 signaling. Furthermore, knockdown of BAMBI was more tumorigenic in HCC cells. Therefore, downregulation of both β-catenin and TGF-β1 signaling by BAMBI might contribute to tumor suppression in mice xenotransplanted with HepG2 or SH-J1 cells. Taken together, ctHBx may have a more oncogenic role than HBx through its inhibition of tumor-suppressive β-catenin/BAMBI signaling.

Mucocutaneous Telangiectasia as a Diagnostic Clue of Hereditary Hemorrhagic Telangiectasia: An Activin Receptor-Like Kinase-1 Mutation in a Korean Patient

No abstract available.

Mucocutaneous Telangiectasia as a Diagnostic Clue of Hereditary Hemorrhagic Telangiectasia: An Activin Receptor-Like Kinase-1 Mutation in a Korean Patient

No abstract available.

Induced differentiation of rat kidney stem cells into renal tubular epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the differentiation capability of kidney stem cells (KSCs) into renal tubular epithelial cells (RTECs).</p><p><b>METHODS</b>KSCs isolated from the renal papilla of 4-week-old SD rats were co-cultured with hypoxia-exposed RTEC in induced medium (containing activin A, BMP-7, and retinoic acid) and renal epithelial cell growth medium (REGM) alternately. The KSCs cultured in MSC medium served as the control. The KSC differentiation rates in both groups were determined using flow cytometry, immunofluorescence assay and qRT-PCR.</p><p><b>RESULTS</b>Flow cytometry showed a CK-18 positive rate of 6.5Percnt; in the control KSC group and of 44.2% in the induced group. Immunofluorescence assay detected the positivity for mature epithelial cell markers CK-18, E-cadherin, and ZO-1 in the induced cells. The results of qRT-PCR showed significantly increased expression of E-cadherin and AQP-1 mRNAs in the induced cells compared with the control cells (P<0.01).</p><p><b>CONCLUSION</b>Rat KSCs can be induced to differentiate into RTECs in vitro.</p>

Treatment of Anovulatory Infertility with Shen Deficiency Syndrome by ZHU's Tiaojing Cuyun Recipe: a Clinical Evaluation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the molecular biological mechanism of ZHU's Tiaojing Cuyun Recipe (TCR) for treating anovulatory infertility patients with Shen deficiency syndrome (SDS) by observing its clinical efficacy.</p><p><b>METHODS</b>Using randomized blocking methods, 80 patients were assigned to the treatment group (40 cases) and the control group (40 cases). Patients with regular menstrual cycle started medication from the 5th day of menstruation. Those with irregular menstrual cycle first took progesterone till withdrawal bleeding ,and then started medication from the 5th day of vaginal bleeding. Patients in the treatment group took ZHU's TCR, one dose per day, while those in the control group took Clomifene Citrate (CC), 50 mg per day. Three menstrual cycles consisted of one therapeutic course, a total of 2 courses. Clinical efficacy such as pregnancy rates and abortion rates were observed. Ovulation indices (the maximal diameter of mature follicles, luteinized follicles, ovulational follicles, and the endometrial thickness on the ovulation day), SDS, and integrals of menstrual symptoms were monitored before and after treatment. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) , and estradiol (E2) were determined using chemiluminescent immunoassay before treatment and after on therapeutic course. Serum levels of activin A (ACTA), inhibin B (INHB), and follistatin (FS) were detected using double antibody sandwich ELISA.</p><p><b>RESULTS</b>Compared with the control group, the pregnancy rate was obviously elevated and the abortion rate was obviously lowered in the treatment group (P <0. 05). Ovulation rates of mature follicles and luteinizing follicles decreased more in the treatment group (P < 0.05). Compared with before treatment, integrals for SDS were lower, the maximal diameter of pre-ovulational follicles was increased, and integrals for menstrual symptoms in non-pregnant patients of the two groups were obviously lowered. Meanwhile, the endometrial thickness on the ovulation day was increased in the treatment group after treatment, but reduced in the control group (P < 0.05, P < 0.01). Compared with the control group, integrals for SDS were decreased, and the maximal diameter of pre-ovulational follicles was lowered in the treatment group after treatment (P < 0.05, P < 0.01). Integrals for SDS and the difference in the endometrial thickness on the ovulation day were increased, but the difference in the maximal diameter of pre-ovulational follicles were reduced (P < 0.05, P < 0.01). In the treatment group serum levels of E2 and ACTA increased more after one therapeutic course than before treatment (P < 0.01), but serum levels of INHB and FS decreased more after one therapeutic course than before treatment (P < 0.05). In the control group serum levels of FSH and ACTA increased more, and the serum level of FS decreased more after one therapeutic course than before treatment (P < 0.05, P < 0.01). Compared with the control group, serum levels of FSH and ACTA increased more, and serum levels of INHB decreased more in the treatment group after one therapeutic course than before treatment (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>ZHU'sTCR could improve SDS of anovulatory infertility patients, regulate the follicular development, and elevate the pregnancy rate. Its actions might be associated with regulating their sex hormones, expressions of ovary local factors such as INHB, ACTA, and FS.</p>

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

Effect of interleukin-1β on expressions of activin A and its related factors in cultured endometrial stromal cells from patients with endometriosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of interleukin-1β (IL-1β) on the expressions activin A, follistatin, and cripto in cultured human endometrial stromal cells (HESCs) form patients with endometriosis.</p><p><b>METHODS</b>Cultured HESCs were stimulated with 250, 500, and 750pg/ml IL-1β, and the mRNA and protein expressions of activin A, follistatin, and cripto were assayed using real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>IL-1β treatment caused significant dose-dependent increments of the mRNA and protein expressions of activin A and follistatin and of the mRNA expression of cripto in cultured HESCs.</p><p><b>CONCLUSION</b>IL-1β can affect the expressions of activin A, follistatin and cripto in HESCs from patients with endometriosis.</p>