ArticleThe Journal of cell biology1998
TGF-beta plays a key role in morphogenesis of the pancreatic islets of Langerhans by controlling the activity of the matrix metalloproteinase MMP-2.
Article in The Journal of cell biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 172 citations in OpenAlex.
- SPOCK2 controls the proliferation and function of immature pancreatic β-cells through MMP2.Experimental & molecular medicine · 2025Article
- PDX1+ cell budding morphogenesis in a stem cell-derived islet spheroid system.Nature communications · 2024Article
- Review
- Fetal Programming of the Endocrine Pancreas: Impact of a Maternal Low-Protein Diet on Gene Expression in the Perinatal Rat Pancreas.International journal of molecular sciences · 2022Article
- Review
- Immune dysfunction in developmental programming of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Article
- Cardiac Glucolipotoxicity and Cardiovascular Outcomes.Medicina (Kaunas, Lithuania) · 2018Review
- A radial axis defined by semaphorin-to-neuropilin signaling controls pancreatic islet morphogenesis.Development (Cambridge, England) · 2017Article
- Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer.Oncotarget · 2017Article
- Expression and localization of matrix metalloproteinases (MMP-2, -7, -9) and their tissue inhibitors (TIMP-2, -3) in the chicken oviduct during maturation.Cell and tissue research · 2016Article
- An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein.Central-European journal of immunology · 2016Article
- Intraislet Pancreatic Ducts Can Give Rise to Insulin-Positive Cells.Endocrinology · 2016Article
- αvβ6 integrin is required for TGFβ1-mediated matrix metalloproteinase2 expression.The Biochemical journal · 2015Article
- Diosgenin attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway.International journal of clinical and experimental medicine · 2015Article
- In vitro pancreas organogenesis from dispersed mouse embryonic progenitors.Journal of visualized experiments : JoVE · 2014Article
- Mesothelin promotes cell proliferation in the remodeling of neonatal rat pancreas.World journal of gastroenterology · 2014Article
- M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Smad signaling pathways regulate pancreatic endocrine development.Developmental biology · 2013Article
- Matrix metalloproteinase-9 reduces islet amyloid formation by degrading islet amyloid polypeptide.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Islets of Langerhans are microorgans scattered throughout the pancreas, and are responsible for synthesizing and secreting pancreatic hormones. While progress has recently been made concerning cell differentiation of the islets of Langerhans, the mechanism controlling islet morphogenesis is not known. It is thought that these islets are formed by mature cell association, first differentiating in the primitive pancreatic epithelium, then migrating in the extracellular matrix, and finally associating into islets of Langerhans. This mechanism suggests that the extracellular matrix has to be degraded for proper islet morphogenesis. We demonstrated in the present study that during rat pancreatic development, matrix metalloproteinase 2 (MMP-2) is activated in vivo between E17 and E19 when islet morphogenesis occurs. We next demonstrated that when E12.5 pancreatic epithelia develop in vitro, MMP-2 is activated in an in vitro model that recapitulates endocrine pancreas development (Miralles, F., P. Czernichow, and R. Scharfmann. 1998. Development. 125: 1017-1024). On the other hand, islet morphogenesis was impaired when MMP-2 activity was inhibited. We next demonstrated that exogenous TGF-beta1 positively controls both islet morphogenesis and MMP-2 activity. Finally, we demonstrated that both islet morphogenesis and MMP-2 activation were abolished in the presence of a pan-specific TGF-beta neutralizing antibody. Taken together, these observations demonstrate that in vitro, TGF-beta is a key activator of pancreatic MMP-2, and that MMP-2 activity is necessary for islet morphogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.