Gastroenterology
Volume 135, Issue 2 , Pages 347-351 , August 2008

Hedgehog Spikes Pancreas Regeneration

  • David A. Cano

      Affiliations

    • Instituto de Biomedicina de Sevilla, Servicio de Endocrinología y Nutrición, Hospitales Universitarios Virgen del Rocío, Sevilla, Spain
    • ,
  • Matthias Hebrok

      Affiliations

    • Diabetes Center, Department of Medicine, University of California, San Francisco, California
    • Corresponding Author InformationAddress requests for reprints to: Matthias Hebrok, Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143; Fax: (415) 564-5813.

References 

  1. Cano DA, Hebrok M, Zenker M. Pancreatic development and disease. Gastroenterology. 2007;132:745–762
  2. Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development. 2002;129:2447–2457
  3. Teta M, Long SY, Wartschow LM, et al. Very slow turnover of beta-cells in aged adult mice. Diabetes. 2005;54:2557–2567
  4. Xu X, D'Hoker J, Stange G, et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell. 2008;132:197–207
  5. Teta M, Rankin MM, Long SY, et al. Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev Cell. 2007;12:817–826
  6. Dor Y, Brown J, Martinez OI, et al. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature. 2004;429:41–46
  7. Bonner-Weir S, Weir GC. New sources of pancreatic beta-cells. Nat Biotechnol. 2005;23:857–861
  8. Bonner-Weir S, Baxter LA, Schuppin GT, et al. A second pathway for regeneration of adult exocrine and endocrine pancreas (A possible recapitulation of embryonic development). Diabetes. 1993;42:1715–1720
  9. Cano DA, Rulifson IC, Heiser PW, et al. Regulated beta-cell regeneration in the adult mouse pancreas. Diabetes. 2008;57:958–966
  10. Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117:2553–2561
  11. Reid LE, Walker NI. Acinar cell apoptosis and the origin of tubular complexes in caerulein-induced pancreatitis. Int J Exp Pathol. 1999;80:205–215
  12. Jensen JN, Cameron E, Garay MV, et al. Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration. Gastroenterology. 2005;128:728–741
  13. Saluja AK, Lerch MM, Phillips PA, et al. Why does pancreatic overstimulation cause pancreatitis?. Annu Rev Physiol. 2007;69:249–269
  14. Strobel O, Dor Y, Alsina J, et al. In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation in inflammatory ductal metaplasia. Gastroenterology. 2007;133:1999–2009
  15. Desai BM, Oliver-Krasinski J, De Leon DD, et al. Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regeneration. J Clin Invest. 2007;117:971–977
  16. Jensen J, Pedersen EE, Galante P, et al. Control of endodermal endocrine development by Hes-1. Nat Genet. 2000;24:36–44
  17. Apelqvist A, Li H, Sommer L, et al. Notch signalling controls pancreatic cell differentiation. Nature. 1999;400:877–881
  18. Esni F, Ghosh B, Biankin AV, et al. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Development. 2004;131:4213–4224
  19. Siveke JT, Lubeseder-Martellato C, Lee M, et al. Notch signaling is required for exocrine regeneration after acute pancreatitis. Gastroenterology. 2008;134:544–555
  20. Fendrich V, Esni F, Garay MV, et al. Hedgehog signaling is required for effective regeneration of exocrine pancreas. Gastroenterology. 2008;135:621–631
  21. Bennett AR, Farley A, Blair NF, et al. Identification and characterization of thymic epithelial progenitor cells. Immunity. 2002;16:803–814
  22. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function?. Cell. 2001;105:829–841
  23. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004;432:324–331
  24. Machold R, Hayashi S, Rutlin M, et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron. 2003;39:937–950
  25. Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 2003;422:313–317
  26. Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004;431:707–712
  27. Trowbridge JJ, Scott MP, Bhatia M. Hedgehog modulates cell cycle regulators in stem cells to control hematopoietic regeneration. Proc Natl Acad Sci U S A. 2006;103:14134–14139
  28. Omenetti A, Diehl AM. The adventures of sonic hedgehog in development and repair (II. Sonic hedgehog and liver development, inflammation, and cancer). Am J Physiol Gastrointest Liver Physiol. 2008;294:G595–G598
  29. Yang L, Wang Y, Mao H, et al. Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells. J Hepatol. 2008;48:98–106
  30. Omenetti A, Yang L, Li YX, et al. Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation. Lab Invest. 2007;87:499–514
  31. Altavilla D, Famulari C, Passaniti M, et al. Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice. Lab Invest. 2003;83:1723–1732
  32. Nakashima H, Nakamura M, Yamaguchi H, et al. Nuclear factor-kappaB contributes to hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer. Cancer Res. 2006;66:7041–7049
  33. Bhanot U, Kohntop R, Hasel C, et al. Evidence of Notch pathway activation in the ectatic ducts of chronic pancreatitis. J Pathol. 2008;214:312–319
  34. Kayed H, Kleeff J, Keleg S, et al. Distribution of Indian Hedgehog and its receptors patched and smoothened in human chronic pancreatitis. J Endocrinol. 2003;178:467–478
  35. Lowenfels AB, Maisonneuve P. Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006;20:197–209
  36. Malka D, Hammel P, Maire F, et al. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut. 2002;51:849–852
  37. Thayer SP, di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003;425:851–856
  38. Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846–851
  39. Guerra C, Mijimolle N, Dhawahir A, et al. Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell. 2003;4:111–120

 Supported by the “Ramón y Cajal” program from the Spanish Ministry of Science and Education (D.C.) and grants from the NIH (DK60533, CA112537 to M.H.).

PII: S0016-5085(08)01184-0

doi: 10.1053/j.gastro.2008.06.063

Gastroenterology
Volume 135, Issue 2 , Pages 347-351 , August 2008

Article Tools

* Image Usage & Resolution