01 September 2005
A word on the possible role of the circulating transforming growth factor ss-1 in hypertension, diabetes, obesity, smoking and human disease involving fibrosis.Shyama Chatterjee, Erick Van Marck
Med Sci Monit 2005; 11(9): LE10-11 :: ID: 428461
Dear Editor, Michael C. Peterson in his review article in the July editionof MSM , suggests that elevated levels of circulating transforming growth factor beta-1 (TGF beta-1)are part of the molecular link between several entities that have epidemiological ties including hypertension,diabetes, smoking and obesity on one hand and diseases resulting in organ fibrosis on the other includingrenal disease and cardiac fibrosis and hypertrophy in heart failure. His hypothesis is that elevatedlevels of TGF beta-1 lead to disease production and to the synergy of risk factors seen in the productionof human fibrotic diseases. Based on this model he predicts that since the presence of TGF beta-1 enhancesfibrosis it might be expected that circulating levels would be a better predictor of the rate of changein disease severity rather than current disease severity. Thus direct inhibitors of TGF beta-1 or genetherapies antagonizing TGF beta-1 will be found useful in humans with hepatic fibrosis from alcoholicliver disease. We would like to supplement some additional data and views on this topic. We are studyingthe immunopathology of liver fibrosis brought about by schistosomiasis. In developing countries, schistosomiasisis a major health problem, which affects at least 200 million individuals, mainly children, with a totalof 600 million people at risk . The major pathological manifestations of this parasitic disease, causedby helminths of the genus Schistosoma, are due to schistosome eggs trapped in the intestinal wall andthe liver of an infected host. Soluble egg antigens (SEA) secreted by miracidia from within the eggsinduce periovular granuloma formation. Hepatosplenic schistosomiasis arises when this granulomatous inflammatoryreaction becomes chronic and disrupts the organ's architecture and circulation, leading to severe hepaticfibrosis, portal hypertension and oesophageal varices, which may rupture and cause fatal bleedings. Wehave studied the neuropeptide somatostatin, a major regulatory peptide of the central nervous systemand the digestive tract, for its potential to modulate the host morbidity caused by parasite infection[3,4]. Our recent work has delineated an association between fibrosis and low levels of endogenous somatostatinplasma levels in Schistosoma mansoni infected subjects [5,6]. Based on these results we have exploredthe therapeutic potential of somatostatin in a mouse model of hepatic fibrosis associated with S. Mansoniinfections, as well as suggested that somatostatin could control variceal bleeding [7,8]. TGF beta-1regulates somatostatin mRNA levels and somatostatin secretion at the hypothalamic level, by significantlyreducing both basal and cAMP-induced somatostatin messenger RNA levels and somatostatin secretion. Thisinhibitory effect is dose-and time-dependent, and requires "de novo" protein synthesis. TGF beta-1 reducesthe stability of somatostatin mRNA, although an additional action on the somatostatin transcription cannotbe discarded. The effects of TGF beta-1 in hypothalamic cultures are direct actions on neurons and notmediated by glial cells. We believe that somatostatin - TGF beta-1 interactions may play a regulatoryrole in the outcome of disease progression in man, via its influence on intersystem signaling. Schistosoma-causedliver morbidity is associated with a 10-fold increase in collagen I mRNA as compared to undiseased situations,and TGF beta-1 mRNA levels rise proportionally to the collagen I mRNA levels during disease. In suchconditions of fibrosis, portal hypertension and variceal bleeding, a direct therapeutic effect of somatostatincan be envisaged due to the presence of somatostatin receptors on the hepatic stellate cells (HSC), wherebysomatostatin could reduce collagen I and III synthesis and alpha smooth muscle actin (SMA) expressionin activated HSC. Circulating low levels of somatostatin and consecutively elevated amounts of TGF beta-1in serum or plasma may be a phenomenon in several human diseases or in disease models. Interactions betweenthe endocrine, nervous and immune system create a network that assists man to fight diseases. Cytokines,hormones and neuropeptides communicate between the three systems forming this network. A good understandingof host pathology requires understanding of this network, which appears to function via communicationand/or reciprocal modulation. Cytokines like TGF beta-1 and neuropeptide hormones like somatostatin (amongstsubstance P and vasoactive intestinal peptide) may constitute one arm of such a network that via communicationsignal host pathological changes during disease. References: 1.Peterson M: Circulating transforming growthfactor beta-1: A partial molecular explanation for associations between hypertension, diabetes, obesity,smoking and human disease involving fibrosis. Med Sci Monit, 2005; 11(7): RA229-RA232 2.Chitsulo L, EngelsD, Montresor A, Savioli L: The global status of schistosomiasis and its control. Acta Trop, 2000; 77:41-51 3.Chatterjee S, Van Marck E: Role of somatostatin in schistosomiasis: A basis for immunomodulationin host-parasite interactions? Trop Med Int Health, 2001; 6: 578-81 4.Chatterjee S, Mbaye A, De Man JG,Van Marck E: Does the neuropeptide somatostatin have therapeutic potential against schistosomiasis? TrendsParasitol, 2002; 18: 295-298 5.Chatterjee S, Mbaye A, Van Marck E: Lower levels of the circulating neuropeptidesomatostatin in S. mansoni infected patients may have pathological significance. Trop Med Int Health,2003; 8: 33-36 6.Chatterjee S, Mbaye A, Alfidja AT et al: Circulating levels of the neuropeptide hormonesomatostatin may determine hepatic fibrosis in Schistosoma mansoni. infections. Acta Trop, 2004; 90:191-203 7.Chatterjee S, Van Marck E: Can somatostatin control acute bleeding from oesophageal varicesin Schistosoma mansoni. i patients? BMC Infect Dis, 2004; 4: 58 8.Chatterjee S, Vrolix G, DepoortereI et al: The therapeutic effect of the neuropeptide hormone somatostatin on Schistosoma mansoni. causedliver fibrosis. BMC Infect Dis, 2005; 5: 45.
Keywords: Diabetes Mellitus - blood, Fibrosis, Hypertension - complications, Obesity - complications, Risk Factors, Schistosomiasis - pathology, Smoking - blood, Somatostatin - blood, Transforming Growth Factor beta - blood, Transforming Growth Factor beta1
01 July 2022 : EditorialEditorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Response to the Global Spread of Lineages and Sublineages of Omicron, or B.1.1.529, SARS-CoV-2
Med Sci Monit 2022; 28:e937676
27 June 2022 : Clinical ResearchShoulder Injury Related to Vaccine Administration (SIRVA) in 16 Patients Following COVID-19 Vaccination Who...
Med Sci Monit In Press; DOI: 10.12659/MSM.937430
04 June 2022 : Clinical ResearchScreening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...
Med Sci Monit 2022; 28:e936962
30 May 2022 : Clinical ResearchEffects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...
Med Sci Monit 2022; 28:e936069
05 Jul 2022 : Clinical ResearchAttention-Deficit/Hyperactivity Disorder (ADHD) and Time Perception in Adults: Do Adults with Different ADH...
Med Sci Monit In Press; DOI: 10.12659/MSM.936849
01 Jul 2022 : Clinical ResearchDoes Early-Period Patient Dissatisfaction Turn Into Satisfaction Over Time After Total Knee Replacement?
Med Sci Monit In Press; DOI: 10.12659/MSM.936792
30 Jun 2022 : Laboratory ResearchBcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human...
Med Sci Monit In Press; DOI: 10.12659/MSM.936760
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788