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Michael B. Sporn

Bio: Michael B. Sporn is an academic researcher from Dartmouth College. The author has contributed to research in topics: Transforming growth factor & Transforming growth factor beta. The author has an hindex of 157, co-authored 559 publications receiving 94605 citations. Previous affiliations of Michael B. Sporn include Cornell University & Reata Pharmaceuticals.


Papers
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Book ChapterDOI
01 Jan 1984
TL;DR: In this paper, the cellular biology and biochemistry of the retinoids are discussed and the effects of retinoid on cell differentiation in many different types of epithelia.
Abstract: Publisher Summary This chapter discusses the cellular biology and biochemistry of the retinoids In isolated 9-day-old rat embryos, retinoic acid prevents the formation of the pharyngeal arches, which are derived from cephalic mesenchyme; these structures later form the maxilla and the mandible Another mesenchymal derivative, whose formation is markedly suppressed by retinoic acid in rat embryos, is the yolk sac circulation Retinoids can exert a powerful influence on cell differentiation in many different types of epithelia The effects of retinoids on differentiation of epithelia in organ culture result from a combination of complex cellular responses and interactions of different cell types in the explant One of the most illuminating examples of the ability of retinoids to promote differentiation is the effect of retinoids on mouse embryonal carcinoma cells These undifferentiated stem cells of teratocarcinomas are multipotential, that is, they can differentiate into a multiplicity of somatic cell types Another example of the ability of retinoic acid to promote terminal differentiation of neoplastic cells to nonneoplastic cell types is the effect of retinoic acid on human promyelocytic leukemia cells

682 citations

Journal ArticleDOI
TL;DR: The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders and provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine.
Abstract: Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine.

664 citations

Journal ArticleDOI
TL;DR: These results demonstrate that both components of the AP-1 complex are required for TGF-beta 1 autoinduction, and may amplify the action of TGF -beta 1 during normal development and oncogenesis.
Abstract: The multifunctional actions of transforming growth factor beta 1 (TGF-beta 1) indicate that it has a pivotal control function in many physiological and pathological processes. An important property of TGF-beta 1 is its ability to activate its own mRNA expression and thereby increase its own secretion. Two distinct regions of the promoter of the TGF-beta 1 gene are responsive to autoregulation: one 5' to the upstream transcriptional start site and another located between the two major start sites. In both promoter regions, autoinduction is mediated by binding of the AP-1 (Jun-Fos) complex. An important contribution to this positive regulation is the autoactivation of c-jun transcription by AP-1. Cotransfection of antisense c-jun or antisense c-fos expression vectors prevents TGF-beta 1 autoinduction. These results demonstrate that both components of the AP-1 complex are required for TGF-beta 1 autoinduction. Induction of jun expression by TGF-beta 1, as well as jun autoinduction, may amplify the action of TGF-beta 1 during normal development and oncogenesis.

664 citations

Journal ArticleDOI
TL;DR: Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs that have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.
Abstract: Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. They are neither conventional cytotoxic agents, nor are they monofunctional drugs that uniquely target single steps in signal transduction pathways. Synthetic oleanane triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the nuclear receptor transcription factors known as retinoid X receptors. Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.

617 citations

Journal ArticleDOI
TL;DR: The importance of developing totally new classes of chemopreventive agents is stressed, with particular emphasis on the potential usefulness of new synthetic triterpenoids derived from naturally occurring molecules.
Abstract: In this short article, we review the conceptual basis for chemoprevention of cancer, the proven clinical efficacy of this concept, and current trends to develop new chemopreventive agents based on understanding of their mechanisms of action. Four classes of new agents, namely selective inhibitors of cyclooxygenase-2, selective estrogen receptor modulators, rexinoids (retinoids that bind selectively to the receptors known as RXRs) and ligands for the peroxisome proliferator-activated receptor-gamma are discussed in detail. The importance of developing totally new classes of chemopreventive agents is stressed, with particular emphasis on the potential usefulness of new synthetic triterpenoids derived from naturally occurring molecules.

595 citations


Cited by
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Journal ArticleDOI
07 Jan 2000-Cell
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.

28,811 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
29 Apr 1993-Nature
TL;DR: The ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

10,861 citations

Journal ArticleDOI
19 Mar 2010-Cell
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.

8,664 citations

Journal ArticleDOI
TL;DR: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms and mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
Abstract: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

7,710 citations