Immunohistochemical Localization of Activin A and Follistatin in Human Tissues.

Wada, Mitsuru; Shintani, Yoshihiro; Kosaka, Masaaki; Sendo, Toshiaki; Hizawa, Kazuo; Saito, Shiro

doi:10.1507/endocrj.43.375

Cited by 77 publications

(55 citation statements)

References 55 publications

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“…Studies have shown that mouse, rat and human pancreatic islet cells produce activin A and follistatin [23,24,29]. We also detected the activin βA subunit, activin type II receptors (actRII and actRIIB) and activin type I receptor (actRIB/alk4) in human islets (data not shown).…”

Section: Resultsmentioning

confidence: 60%

“…Conversely, follistatin completely reversed the dedifferentiating effects of activin A. Both activin A and follistatin are produced in islets [23,24], suggesting paracrine control of beta cell maturity. Interestingly, a preliminary experiment showed that levels of the activin βA subunit were increased in human islets treated with activin A (M. Szabat, unpublished data), supporting a positive feedback for autocrine or paracrine regulation of activin A expression.…”

Section: Discussionmentioning

confidence: 91%

“…Activins and their receptors are present in the developing pancreas and adult islet cells [23,24]. Follistatin, a potent endogenous activin antagonist, is also produced in adult islets [23,24]. These observations suggest that activins may play dynamic, tightly controlled autocrine and/or paracrine roles in adult islets.…”

Section: Introductionmentioning

confidence: 97%

“…Activins control embryonic patterning of foregut-derived organs [19], have important roles in pancreatic development [20] and have been implicated in the control of insulin secretion [21,22]. Activins and their receptors are present in the developing pancreas and adult islet cells [23,24]. Follistatin, a potent endogenous activin antagonist, is also produced in adult islets [23,24].…”

Section: Introductionmentioning

confidence: 99%

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Reciprocal modulation of adult beta cell maturity by activin A and follistatin

2010

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Aims/hypothesis The functional maturity of pancreatic beta cells is impaired in diabetes mellitus. We sought to define factors that can influence adult beta cell maturation status and function. Methods MIN6 cells labelled with a Pdx1 monomeric red fluorescent protein-Ins1 enhanced green fluorescent protein dual reporter lentivirus were used to screen candidate growth and/or differentiation factors using image-based approaches with confirmation by real-time RT-PCR and assays of beta cell function using primary mouse islets.Results Activin A strikingly decreased the number of mature beta cells and increased the number of immature beta cells. While activins are critical for pancreatic morphogenesis, their role in adult beta cells remains controversial. In primary islets and MIN6 cells, activin A significantly decreased the expression of insulin and several genes associated with beta cell maturity (e.g. Pdx1, Mafa, Glut2 [also known as Slc2a2]). Genes found in immature beta cells (e.g. Mafb) tended to be upregulated by activin A. Insulin secretion was also reduced by activin A. In addition, activin A-treated MIN6 cells proliferated faster than non-treated cells. The effects of endogenous activin A on beta cells were completely reversed by exogenous follistatin. Conclusions/interpretation These results suggest that autocrine and/or paracrine activin A signalling exerts a suppressive effect on adult beta cell maturation and function. Thus, the maturation state of adult beta cells can be modulated by external factors in culture. Interventions inhibiting activin or its signalling pathways may improve beta cell function. Understanding of maturation and plasticity of adult pancreatic tissue has significant implications for islet regeneration and for in vitro generation of functional beta cells.

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Section: Resultsmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Reciprocal modulation of adult beta cell maturity by activin A and follistatin

2010

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“…At the same time, primordial through to primary follicles do not express follistatin mRNA (Kogawa et al, 1991;Braw-Tal, 1994;Tisdall et al, 1994), implying that follistatin may not be involved in the initial stage of recruitment of follicles. Species differences occur, as the expression of follistatin is maintained in the corpus luteum in primates, whereas in other species, expression falls markedly after ovulation in the developing corpus luteum (Kogawa et al, 1991;Roberts et al, 1993;Wada et al, 1996).…”

Section: Location and Secretion Of Follistatinmentioning

confidence: 99%

Regulation of ovarian function by the TGF-beta superfamily and follistatin

et al. 2003

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The role of follistatin as an activin-binding protein has dominated the study of this molecule for the last 10 years. However, there is emerging evidence that follistatin has a role in modulating the biology of other members of the transforming growth factor beta (TGF-beta) superfamily. This review summarizes the current concepts encompassing follistatin biochemistry as well as molecules with which it is functionally associated. Moreover, the importance of the two follistatin isoforms (follistatin-288 and follistatin-315) is discussed with particular emphasis on the regulation of the ovary. In addition to activin, this review discusses the functions of other members of the TGF-beta superfamily, for example growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), BMP-6, BMP-4 and BMP-7, in the ovary, and the potential interactions between follistatin and these growth factors. The complex network of TGF-beta superfamily growth factor members involved in the modulation of ovarian function and the interactions of follistatin with these proteins is highlighted.

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Localization of an activin/activin receptor system in the porcine ovary

Hurk

Pavert

2001

Molecular Reproduction Devel

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The aim of this study was to locate a possible activin/activin receptor system within porcine ovaries containing functional corpora lutea. In situ hybridization was used to assess the gene expression of beta(A)- and beta(B)-activin subunits, and immunohistochemical studies were done to detect activin-A protein and activin receptor type II. mRNA expression of the beta(A)- and beta(B)-activin subunits was found in the granulosa from the unilaminar follicle stage onward, in the developing thecal layer of multilaminar and small antral follicles, in the theca interna of mid-sized antral follicles, in corpora lutea, and in the ovarian surface epithelium. Immunoreactive activin A protein could be detected at the same ovarian sites, but in thecal tissue of small antral follicles only. This protein was also demonstrated at the peripheral zone of oocytes from multilaminar and antral follicles. A positive immunoreaction for activin receptor was found in granulosa cells from multilaminar and older follicles and in oocytes from the earliest stages of follicular development onward. In late multilaminar follicles and in antral follicles, the oolemma was stained. Except for small antral follicles, a positive activin receptor immunoreaction was absent in the follicular theca. Activin receptor immunoreaction was furthermore present in corpora lutea and in the ovarian surface epithelium. It is concluded that, within porcine ovaries containing functional corpora lutea, an activin/activin receptor system is present in all intact follicles, the corpora lutea and the surface epithelium. Within follicles, granulosa and theca cells are the main sites of activin synthesis, while oocytes and granulosa cells are the main activin binding sites.

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Immunohistochemical Localization of Activin A and Follistatin in Human Tissues.

Abstract: Abstract.We immunohistochemically investigated the localization of activin A and follistatin in various human tissues with specific antibodies to recombinant human (rh-) activin A and rh-follistatin.

Cited by 77 publications

References 55 publications

Reciprocal modulation of adult beta cell maturity by activin A and follistatin

Reciprocal modulation of adult beta cell maturity by activin A and follistatin

Regulation of ovarian function by the TGF-beta superfamily and follistatin

Localization of an activin/activin receptor system in the porcine ovary

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