IN EXPERIMENTAL RAT DIABETES TRANSCRIPTION FACTOR MAFA IS SYNTHESIZED IN DIFFERENTIATED PANCREATIC ISLET CELLS AND DOES NOT SERVE AS A MARKER OF PROGENITOR CELLS



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Different transcription factors, which are synthesized at different stages of cell differentiation, are often considered markers of p-cell precursors. One of these transcription factors is MafA, the role of which is not fully understood. According to one hypothesis, it activates insulin gene expression in the differentiating p-cells. According to another, this factor is only necessary for the regulation of insulin secretion by already differentiated p-cells. In favor of the latter hypothesis, we showed that MafA is not expressed in the immature p-cells during the prenatal development of the human pancreas. In order to finally determine whether MafA is a marker of differentiating cells or it is synthesized in already mature p-cells the aim of our investigation was the analysis of dynamical changes of MafA-positive cell population and C-kit-positive endocrinocyte precursors in Langerhans islets during experimental diabetes in rats. The study was performed on male Wistar rats (250-300g body weight) which were intraperitoneally injected with alloxan. Animals were sacrificed 1,2, 7, 14, 21 days of the experiment for the morphological analysis of pancreas. Paraffin sections of pancreas were stained immunohistochemically with antibodies against MafA, C-kit, insulin and glucagon. The maximum number of MafA-positive cells in the islets was found during normal prenatal development of pancreas. At all stages of the experimental diabetes the number of MafA-positive cells in the islets decreased, wherein the number of insulin-positive cells in the islets increased by the end of the first and third weeks of the experiment. It was also established that in experimental diabetes, changes in populations of MafA- and C-kit-positive cells occur in different ways. Thus, the results of our research showed that MafA cannot be considered as a marker of progenitor cells and is expressed only in the mature cells of the Langerhans islets, that confirms our previous data obtained during the study of prenatal development of human pancreas.

Full Text

Restricted Access

About the authors

M. S Kaligin

Kazan (Volga Region) Federal University

Email: mfkaligin@mail.ru
Kazan, Russia

A. A Titova

Kazan (Volga Region) Federal University

Kazan, Russia

D. I Andreeva

Kazan (Volga Region) Federal University

Kazan, Russia

M. A Titova

Kazan (Volga Region) Federal University

Kazan, Russia

A. A Gumerova

Kazan (Volga Region) Federal University

Kazan, Russia

A. P Kiyasov

Kazan (Volga Region) Federal University

Kazan, Russia

References

  1. Whiting D.R., Guariguata L., Weil C. et al. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res. Clin. Pract. 2011; 94: 311-21.
  2. Olbrot M., Rud J., Moss L.G. et al. Identification of beta -cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. PNAS USA 2002; 99: 6737-42.
  3. Kataoka K., Han S.I., Shioda S. et al. MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. J. Biol. Chem. 2002; 277: 49903-10.
  4. Sharma A., Stein R. Glucose-induced transcription of the insulin gene is mediated by factors required for B-cell-typespecificexpression. Mol. Cell. Biol. 1994; 14: 871-9.
  5. Matsuoka T.A., Zhao L., Artner I. et al. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol. Cell. Biol. 2003; 23: 6049-62.
  6. Artner I., Blanchi B., Raum J.C. et al. MafB is required for islet cell maturation. PNAS USA 2007; 104: 3853-8.
  7. Zhao L., Guo M., Matsuoka T.A. et al. The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription. J. Biol. Chem. 2005; 280: 11887-94.
  8. Hang Y., Stein R. MafA and MafB activity in pancreatic beta cells. Trends Endocrinol. Metab. 2011; 22: 364-73.
  9. Hu H.K., Juhl K., Karadimos M. Differentiation of pancreatic endocrine progenitors reversibly blocked by premature induction of MafA. Dev. Biol. 2014; 385: 2-12.
  10. Matsuoka T.A., Artner I., Henderson E. et al. The MafA transcription factor appears to be responsible for tissue specific expression of insulin. PNAS USA 2004; 101: 2930-3.
  11. Zhang C., Moriguchi T., Kajihara M. et al. MafA is a key regulator of glucose-stimulated insulin secretion. Mol. Cell. Biol. 2005; 25: 4969-76.
  12. Aguayo-Mazzucato C., Koh A., Khattabi I. et al. Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells. Diabetologia 2011; 54: 583-93.
  13. Hang Y., Yamamoto T., Benninger R.K. et al. The MafA transcription factor becomes essential to islet beta-cells soon after birth. Diabetes 2014; 63: 1994-2005.
  14. Sui L., Danzl N., Campbell S.R. et al. p-Cell Replacement in mice using human type 1 diabetes nuclear transfer embryonic stem cells. Diabetes 2018; 67: 26-35.
  15. Iacovazzo D., Flanagan S.E., Walker E. et al. MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. PNAS USA 2018; 115(5): 1027-32.
  16. Kaligin M., Pliushkina A., Titova A. et al. Population dynamics of MafA-positive cells during ontogeny of human pancreas. BioNanoScience 2017; 7(2): 352-9.
  17. Плюшкина А.С., Калигин М.С., Андреева Д.И. и соавт. C-kit-позитивные клетки островков поджелудочной железы крысы как клетки-предшественницы эндокриноцитов при аллоксановом диабете. Клеточная трансплантология и тканевая инженерия 2012; VII(3): 138-41. [Plushkina A.S., Kaligin M.S., Andreeva D.I. et al. C-kit-positive pancreas islets cell of rats pancreas as a endocrine cells progenitor during alloxan diabetes. Cellular Transplantation and Tissue Engineering 2012; VII(3): 138-41. (In Russ.)].
  18. Robb P. The development of the islets of Langerhans in the human foetus. Q.J. Exp. Physiol. Cogn. Med. Sci. 1961; 46: 335-43.
  19. Kaligin M.S., Pliushkina A.S., Titova A.A. et al. C-Kit expression as a feature of functional differentiation of progenitor cells. Res. J. Pharm. Biol. Chem. Sci. 2015; 6: 2175-83.
  20. Закирьянов А.Р., Великий Д.А., Онищенко Н.А. и соавт. Способ моделирования сахарного диабета I типа у крыс. Патент РФ на изобретение № 2400822. 22 мая 2009.
  21. Abdellatif A.M., Ogata K., Kudo T. et al. Role of large MAF transcription factors in the mouse endocrine pancreas. Exp. Anim. 2015; 64: 305-12.
  22. Wang H., Brun T., Kataoka K. et al. MAFA controls genes implicated in insulin biosynthesis and secretion. Diabetologia 2007; 50: 348-58.
  23. Bell G.I., Kayano T., Buse J.B. et al. Molecular biology of mammalian glucose transporters. Diabetes Care 1990; 13: 198-208.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies