Endoscopic and pathological features of neoplastic transformation of gastric hyperplastic polyps:Retrospective study of 4010 cases

BACKGROUND Hyperplastic polyps,which represent 30%-93%of all gastric epithelial polyps,are the second most common type of gastric polyps after fundic gland polyps.They were previously considered to have no risk of neoplastic transformation.Recently,an increasing number of cases of gastric hyperplastic polyps(GHPs)combined with neoplastic changes have been reported;however,the specific mechanism underlying their transformation has not been thoroughly explored.AIM To investigate the clinical,endoscopic,and pathological characteristics of the neoplastic transformation of GHPs and explore the risk factors.METHODS A retrospective analysis was performed on 4010 cases of GHPs diagnosed by gastroscopy and pathological examination at the hospital from 2005 to 2021.In total,3874,119,and 17 cases were in the group without intraepithelial neoplasia(IN),with low-grade IN,and with high-grade IN,respectively.The data analysis examined the association of endoscopic and pathological features with risk factors for neoplastic transformation.Factors with significant differences were entered into univariate logistic regression,followed by multivariate logistic regression analysis.RESULTS Univariate analysis revealed diameter,multiple polyp presence,redness,rough surface,lobulation,erosion,Yamada classification,location,and gastric mucosa were risk factors for neoplastic transformation.Multivariate analysis showed that age>65 years[odds ratio(OR)=1.789;95%confidence interval(CI):1.227-2.609;P=0.003],male sex(OR=1.680;95%CI:1.158-2.438;P=0.006),multiple polyps(OR=1.851;95%CI:1.230-2.784;P=0.003),pedunculated or semi-pedunculated shape(OR=2.722;95%CI:1.689-4.388;P<0.001),and polyp diameter were significantly associated with GHPs that demonstrated neoplastic transformation.Compared with chronic superficial gastritis,autoimmune gastritis,atrophic gastritis,and gastritis with IN were independent risk factors for neoplastic transformation[(OR=2.672;95%CI:1.559-4.579;P<0.001),(OR=1.876;95%CI:1.134-3.103;P=0.014),and(OR=5.299;95%CI:3.173–8.849;P<0.001),respectively].CONCLUSION Male sex,age>65 years,multiple polyps,pedunculated or semi-pedunculated shape,polyp size>1 cm,and specific background gastric mucosa are key indicators for predicting neoplastic transformation of GHPs.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor β type Ⅱ receptor

BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway.AIM To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis.METHODS Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8(CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect.RESULTS We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine(DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson’s trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver.CONCLUSION DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

Malignant Transformation and Abnormal Expression of Eukaryotic Initiation Factor in Bronchial Epithelial Cells Induced by Cadmium Chloride

Objective To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 （eIF3 p36） in human bronchial epithelial （16HBE） cells induced by cadmium chloride （CdCl2）. Methods 16HBE cells were treated several times with different concentrations of CdCl2. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdC12, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique （FQ-PCR）. Results The 35th passage of 16HBE cells transformed by CdCl2 exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects （P〈0.01）. All Cd-induced transformed cell lines formed rumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl2 were elevated as compared with the non-transformed control （P〈0.01）, and the eIF3 expression increased with the degree of cell malignancy. Conclusion CdCl2 is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2 and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Factors Affecting Transformation Temperatures in Fe-Mn-Si-Cr-Ni Shape Memory Alloy

The effects of prestrain and annealing temperature on phase transformation temperatures in Fel4Mn5Si8Cr4Ni shape memory alloy have been studied. The results showed that when the annealing temperature was 673 K, both the At and the Ms temperatures increased appreciably as the prestrain increased, the As temperature increased slightly with increasing prestrain; the resistivity difference at 303 K between the heating and cooling curve also increased with increasing prestrain, which agreed with the recovery strain. The shape memory effect in Fe-Mn-Si-Cr-Ni shape memory alloy is caused by the stress-induced γ→ε martensite transformation and its reverse transformation. When the prestrain was 10%, the Ms temperature decreased remarkably as the annealing temperature increased.

T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.

The Factors for Transformation between the Fractions of Speciation of Trace Metals in Lake Sediments

Objective Despite the fact that the bioavailability of trace metals indicated by their speciation has been an indispensable parameter in the assessment and treatment of the environmental pollution of trace metals, many studies have suggested that the bioavailability of trace metals may change according to the conditions of the environment, and the speciation of trace metals can also transform between some fractions. These transformations are related with these factors such as the compositions, microorganism, time, and other physical-chemical conditions of the system. Our work aims to systematically investigate and probe the factors to affect the transformation aside from analysis at certain time-place. The results of these understanding and investigations can be used for reasonably determining the allocation of financial and technical resources in natural and engineered processes, with bringing about inspirations from the evolution of the speciation of the trace metals on environmental impacts.

Simultaneous Determination of Rare Earth Elements by Dual-System Iterative Target Transformation Factor Analysis

Dualcolor systems were used to reduce the collinearity of multicomponent spectra, which is described by the angles between spectra vectors. Combined with iterative target transformation factor analysis, single rare earth element was determined in its mixture. The calculated results show that the average angle between rare earth spectra in one color system(trichloroarsenazorare earths, pH 34) is 45, and that in two color systems(trichloroarsenazorare earths, pH 34, 14) is 215. This technique makes it easy to select the real number of the components in mixtures, and the determination results show dualcolor system method is an effective technique in rare earth mixture analysis.

Advanced lung adenocarcinoma with EGFR 19-del mutation transforms into squamous cell carcinoma after EGFR tyrosine kinase inhibitor treatment

In this editorial we comment on the article by Ji et al.We focus specifically on the EGFR tyrosine kinase inhibitor(EGFR-TKI)treatment and the development of drug resistance to EGFR-TKIs.

What Drives China’s Transformational Growth:Technology,Efficiency or Factor Cost?

With rising costs of capital, labor and energy, cost efficiency and cost management have become important questions confronting the next stage of China＇s economic growth. By building a parametric cost frontier model using panel data, this paper investigates the drivers of economic growth transformation from a cost perspective. According to our research, among various effects triggering corporate cost variations and in addition to the expansion of production scale, the largest effect is from technological progress, followed by the effect of factor price adjustment and the effect of efficiency gains. Within the decomposition of factor price adjustment effect, the energy factor effect is the most significant. Furthermore, energy price fluctuations are likely to become major factors restricting saving-based growth. Further study reveals that both the ownership reform and opening up of SOEs are favorable to reducing the costs generated by inefficiency. This paper provides empirical evidence for the driving mechanism of saving-based growth transformation as well as empirical evidence to support to the further deepening of property rights and market-oriented reforms.

Alterative Expression and Sequence of Human Elongation Factor-1δ during Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cadmium Chloride

Objective To study the alternative expression and sequence of human elongation factor-1δ （human EF-1δ p31） during malignant transformation of human bronchial epithelial cells induced by cadmium chloride （CdCl2） and its possible mechanism. Methods Total RNA was isolated at different stages of transformed human bronchial epithelial cells （16HBE） induced by CdCl2 at a concentration of 5.0 μM. Special primers and probe for human EF-1δ p31 were designed and expression of human EF-18 mRNA from different cell lines was detected with fluorescent quantitative PCR technique. EF-18 cDNA from different cell lines was purified and cloned into pMD 18-T vector followed by confirming and sequencing analysis. Results The expressions of human EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2 was elevated （P〈0.01 or P〈0.05）. Compared with their corresponding non-transformed ceils, the overexpression level of EF-15 p31 was averagely increased 2.9 folds in Cd-pretransformed cells, 4.3 folds in Cd-transformed ceils and 7.2 folds in Cd-tumorigenic cells. No change was found in the sequence of overexpressed EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2. Conclusion Overexpression of human EF-1δ p31 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2, but is not correlated with DNA mutations.

Online Capacitor Voltage Transformer Measurement Error State Evaluation Method Based on In-Phase Relationship and Abnormal Point Detection

The assessment of the measurement error status of online Capacitor Voltage Transformers (CVT) within the power grid is of profound significance to the equitable trade of electric energy and the secure operation of the power grid. This paper advances an online CVT error state evaluation method, anchored in the in-phase relationship and outlier detection. Initially, this method leverages the in-phase relationship to obviate the influence of primary side fluctuations in the grid on assessment accuracy. Subsequently, Principal Component Analysis (PCA) is employed to meticulously disentangle the error change information inherent in the CVT from the measured values and to compute statistics that delineate the error state. Finally, the Local Outlier Factor (LOF) is deployed to discern outliers in the statistics, with thresholds serving to appraise the CVT error state. Experimental results incontrovertibly demonstrate the efficacy of this method, showcasing its prowess in effecting online tracking of CVT error changes and conducting error state assessments. The discernible enhancements in reliability, accuracy, and sensitivity are manifest, with the assessment accuracy reaching an exemplary 0.01%.

Study on risk factors of hemorrhagic transformation in patients with acute cerebral infarction after non thrombolysis

Objective:To study the risk factors of hemorrhagic transformation in patients with acute cerebral infarction and to analyze the risk factors.Methods: A total of 96 patients with acute cerebral infarction after the thrombolysis in our hospital from June 2016 to December 2017 were selected as the research object. And they were divided into bleeding group 48 cases and hemorrhage transformation group 48 cases according to whether with hemorrhage occurs transformation. Then the lipid metabolism, atrial fibrillation, history of smoking and drinking, history of hypertension and diabetes, blood pressure, treatment time after onset and infarction area of two groups were compared, and the relationship between those factors and the disease were analyzed by the multi-factor Logistic regression analysis.Results: The atrial fibrillation, history of smoking and drinking of two groups had significant differences;The hospital fasting plasma glucose and LDL-C level of two groups had significant differences;the treatment time after onset and infarction area of two groups had significant differences;The multi-factor Logistic regression analysis showed that atrial fibrillation, blood glucose on admission, LDL-C and large area of infarction are the factors affecting the risk of bleeding in patients with acute cerebral infarction transformation.Conclusion:Atrial fibrillation, blood glucose on admission, LDL-C, treatment time after onset and large area of infarction belongs to the patients with acute cerebral infarction after the thrombolysis transformation of bleeding risk factors.

Plasma Levels of Transforming Growth Factor-Beta 1 in Women with Pelvic Organ Prolapse

Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in patients with POP, so it is unknown whether they are also changed or not. Therefore, we compared plasma TGF-β1 levels in women with and without POP. Methods: Participants were 49 women with POP and 23 healthy control women. All participants were postmenopausal. We measured plasma TGF-β1 and compared data between patients with POP and controls, and between patients with uterine prolapse (UP, n = 19) and those with a cystocele (CC, n = 30). In addition, in patients, we assessed the POP quantification system (POP-Q) stage. Results: Plasma TGF-β1 levels were significantly lower in patients than in healthy controls. POP-Q stage was not significantly different between the UP and CC subgroups, but POP-Q stage IV was diagnosed in 63% of patients with UP and 7% of those with CC. Plasma TGF-β1 levels were significantly lower in the CC subgroup than in the UP subgroup. Conclusion: Plasma TGF-β1 is decreased in POP. It remains unclear whether the lower levels indicate a reduction in systemic TGF-β1 activity, but they can be assumed to reflect reduced TGF-β1 expression in POP tissues.

考虑多维影响因素的改进Transformer-PSO短期电价预测方法

随着多元化电力市场的建设,电价影响因素日益增加,市场环境变化也更加剧烈.为提高市场短期电价的预测精度,提出一种考虑多种电价影响因素的改进Transformer-粒子群优化(PSO)算法短期电价预测方法.首先,在考虑历史电价、负荷的基础上进一步分析电价形成的相关因素,利用自相关函数分析电价的多周期特性并在此基础上调整输入序列,克服了仅采用历史数据以及经验调整输入序列导致预测精度受限的问题.其次,结合长短期记忆(LSTM)、自注意力机制与多层注意力机制并采用多输入结构建立改进Transformer模型,进一步提升LSTM模型捕获不同时间步信息间的长短期依赖关系的能力,克服LSTM的信息利用瓶颈,适应包括历史电价及多种电价成因的复杂多序列输入.此外,还利用PSO智能算法搜索模型不同学习阶段的最佳学习率克服手动调整学习率的局限性.最后,采用PJM市场电价进行算例分析,结果表明所提短期电价预测模型能应用于电价影响因素多、变化剧烈的市场环境,并有效提升短期电价预测精度.

Effect of intestinal ischemia-reperfusion on expressions of endogenous basic fibroblast growth factor and transforming growth factor β in lung and its relation with lung repair

AIM To study the changes of endogenoustransforming growth factor β(TGFβ)and basicfibroblast growth factor(bFGF)in lung followingintestinal ischemia and reperfusion injury andtheir effects on lung injury and repair.METHODS Sixty Wistar rats were divided intofive groups,which underwent sham-operation,ischemia(45 minutes),and reperfusion(6,24and 48 hours,respectively)after ischemia(45minutes).Immunohistochemical method wasused to observe the localization and amounts ofboth growth factors.RESULTS Positive signals of both growthfactors could be found in normal lung,mainly inalveolar cells and endothelial cells of vein.Afterischemia and reperfusion insult,expressions ofboth growth factors were increased and theiramounts at 6 hours were larger than those ofnormal control or of 24 and 48 hours after insult.CONCLUSION The endogenous bFGF and TGF βexpression appears to be up-regulated in thelung following intestinal ischemia andreperfusion,suggesting that both growth factorsmay be involved in the process of lung injury andrepair.

Stage-specific localization of transforming growth factor β1 and β3 and their receptors during spermatogenesis in men

Aim: To investigate the stage-specific localization of transforming growth factor (TGF) β1 and β3 during spermatogenesis in adult human testis. Methods: The localization of TGFβ1 and β3 was investigated by immunohis tochemical staining method employing specific polyclonal antibodies. Results: Both TGFβ1 and β3 and their recep tors were preponderant in the Leydig celis. TGFβ1 could not be detected in the seminiferous tubules. TGFβ3 and TGFβ-Receptor (R) I were mainly seen in the elongated spermatids, while TGFβ-RⅡ in the pachytene spermatocytes and weak in the spermatogonia, spermatids and Sertoli celis. Only TGFβ-RⅡ was detected in the Sertoli celis. TGFβ3, TGFβ-RⅠ and TGFβ-RⅡ showed a staining pattern dependent upon the stages of the seminiferous epithelium cycle. Conclusion: TGFβ isoforms and their receptors are present in the somatic and germ celis of the adult human testis, suggesting their involvement in the regulation of spermatogenesis.

Effect of matrine on transforming growth factor β1 and hepatocyte growth factor in rat liver fibrosis model

Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after treatment.Six rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups.Results:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P<0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P<0.05);group D showed a lowest level of TGF-β1,followed by groups C and B.HGF of group B decreased more significantly than A group at weeks 4 and 8(P<0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P<0.05),in which the group D showed the highest level of HGF.According to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement.Conclusions:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats.

Transforming growth factor-β and fibrosis

Transforming growth factor-β （TGF-β）, a prototype of multifunctional cytokine, is a key regulator of extracellular matrix （ECM） assembly and remodeling. Specifically, TGF-β isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-β expression in affected organs, and subsequent deregulation of TGF-β functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-β receptors. In particular, Smad proteins, TGF-β receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of type I collagen gene expression and in the development of fibrosis, demonstrated both/n vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes.