Match!

Macrophages are essential for CTGF-mediated adult β-cell proliferation after injury.

Published on Aug 1, 2015in Molecular metabolism6.18
· DOI :10.1016/j.molmet.2015.05.002
Kimberly G. Riley2
Estimated H-index: 2
(Vandy: Vanderbilt University),
Raymond C. Pasek9
Estimated H-index: 9
(Vandy: Vanderbilt University)
+ 5 AuthorsMaureen Gannon37
Estimated H-index: 37
Cite
Abstract
Objective Promotion of endogenous β-cell mass expansion could facilitate regeneration in patients with diabetes. We discovered that the secreted protein CTGF (aka CCN2) promotes adult β-cell replication and mass regeneration after injury via increasing β-cell immaturity and shortening the replicative refractory period. However, the mechanism of CTGF-mediated β-cell proliferation is unknown. Here we focused on whether CTGF alters cells of the immune system to enhance β-cell replication.
  • References (30)
  • Citations (21)
Cite
References30
Newest
Published on Apr 1, 2015in Diabetes7.20
Kimberly G. Riley2
Estimated H-index: 2
(Vandy: Vanderbilt University),
Raymond C. Pasek9
Estimated H-index: 9
(Vandy: Vanderbilt University)
+ 5 AuthorsMaureen Gannon37
Estimated H-index: 37
Stimulation of endogenous β-cell expansion could facilitate regeneration in patients with diabetes. In mice, connective tissue growth factor (CTGF) is expressed in embryonic β-cells and in adult β-cells during periods of expansion. We discovered that in embryos CTGF is necessary for β-cell proliferation, and increased CTGF in β-cells promotes proliferation of immature (MafA−) insulin-positive cells. CTGF overexpression, under nonstimulatory conditions, does not increase adult β-cell proliferatio...
Published on Apr 1, 2014in Immunology4.15
Alyssa Charrier9
Estimated H-index: 9
(OSU: Ohio State University),
Ruju Chen7
Estimated H-index: 7
(The Research Institute at Nationwide Children's Hospital)
+ 1 AuthorsDavid R. Brigstock37
Estimated H-index: 37
(OSU: Ohio State University)
Pancreatitis is caused by long-term heavy alcohol consumption, which results in injury and death of pancreatic acinar cells (PAC). The PAC play a pivotal role in mediating early inflammatory responses but the underlying mechanisms remain poorly understood. Treatment of C57BL/6 mice with ethanol and cerulein resulted in increased staining for acinar interleukin-1β (IL-1β), chemokine (C-C motif) ligand 3 (CCL3), or connective tissue growth factor (CTGF/CCN2) by Day 16 and this was associated with ...
Xiangwei Xiao14
Estimated H-index: 14
(University of Pittsburgh),
Iljana Gaffar7
Estimated H-index: 7
(University of Pittsburgh)
+ 8 AuthorsChiyo Shiota15
Estimated H-index: 15
(University of Pittsburgh)
Determination of signaling pathways that regulate beta-cell replication is critical for beta-cell therapy. Here, we show that blocking pancreatic macrophage infiltration after pancreatic duct ligation (PDL) completely inhibits beta-cell proliferation. The TGFβ superfamily signaling inhibitor SMAD7 was significantly up-regulated in beta cells after PDL. Beta cells failed to proliferate in response to PDL in beta-cell–specific SMAD7 mutant mice. Forced expression of SMAD7 in beta cells by itself w...
Published on Mar 1, 2014in Cell Metabolism22.41
Marcela Brissova28
Estimated H-index: 28
(VUMC: Vanderbilt University Medical Center),
Kristie Aamodt9
Estimated H-index: 9
(VUMC: Vanderbilt University Medical Center)
+ 9 AuthorsRadhika Aramandla7
Estimated H-index: 7
(VUMC: Vanderbilt University Medical Center)
Summary Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature, islet microenvironment, and β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to β cell loss. After w...
Published on Jan 1, 2014in Diabetes7.20
Ercument Dirice16
Estimated H-index: 16
(Harvard University),
Sevim Kahraman7
Estimated H-index: 7
(Harvard University)
+ 8 AuthorsDiane Mathis113
Estimated H-index: 113
(Harvard University)
Type 1 diabetes is characterized by infiltration of pancreatic islets with immune cells, leading to insulin deficiency. Although infiltrating immune cells are traditionally considered to negatively impact β-cells by promoting their death, their contribution to proliferation is not fully understood. Here we report that islets exhibiting insulitis also manifested proliferation of β-cells that positively correlated with the extent of lymphocyte infiltration. Adoptive transfer of diabetogenic CD4+ a...
Published on Jan 1, 2013in Laboratory Investigation3.68
Maria P. Alfaro9
Estimated H-index: 9
,
Desirae L. Deskins6
Estimated H-index: 6
+ 6 AuthorsPampee P. Young27
Estimated H-index: 27
Mesenchymal stem cells (MSCs) that overexpress secreted frizzled-related protein 2 (sFRP2) exhibit an enhanced reparative phenotype. The secretomes of sFRP2-overexpressing MSCs and vector control-MSCs were compared through liquid chromatography tandem mass spectrometry. Proteomic profiling revealed that connective tissue growth factor (CTGF; CCN2) was overrepresented in the conditioned media of sFRP2-overexpressing MSCs and MSC-derived CTGF could thus be an important paracrine effector. Subcutan...
Published on Jul 1, 2012in Cell Cycle3.26
Uma Gunasekaran5
Estimated H-index: 5
(VUMC: Vanderbilt University Medical Center),
Courtney W. Hudgens2
Estimated H-index: 2
(VUMC: Vanderbilt University Medical Center)
+ 2 AuthorsMaureen Gannon37
Estimated H-index: 37
(VUMC: Vanderbilt University Medical Center)
Diabetes results from an inadequate functional β cell mass, either due to autoimmune destruction (Type 1 diabetes) or insulin resistance combined with β cell failure (Type 2 diabetes). Strategies to enhance β cell regeneration or increase cell proliferation could improve outcomes for patients with diabetes. Research conducted over the past several years has revealed that factors regulating embryonic β cell mass expansion differ from those regulating replication ofβ cells post-weaning. This artic...
Michelle A. Guney5
Estimated H-index: 5
,
Christine P. Petersen8
Estimated H-index: 8
+ 8 AuthorsAris N. Economides46
Estimated H-index: 46
(Regeneron)
Type 1 and type 2 diabetes result from an absolute or relative reduction in functional β-cell mass. One approach to replacing lost β-cell mass is transplantation of cadaveric islets; however, this approach is limited by lack of adequate donor tissue. Therefore, there is much interest in identifying factors that enhance β-cell differentiation and proliferation in vivo or in vitro. Connective tissue growth factor (CTGF) is a secreted molecule expressed in endothelial cells, pancreatic ducts, and e...
Published on Apr 22, 2010in Nature43.07
Fabrizio Thorel20
Estimated H-index: 20
,
Népote1
Estimated H-index: 1
+ 4 AuthorsPedro Luis Herrera50
Estimated H-index: 50
Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. H...
Published on Apr 1, 2010in Nature43.07
Fabrizio Thorel20
Estimated H-index: 20
,
Virginie Nepote6
Estimated H-index: 6
+ 4 AuthorsPedro Luis Herrera50
Estimated H-index: 50
In the pancreas, insulin-producing β-cells are long-lived and generally replicate seldom. They can do so, however, after increased metabolic demand or after injury. Here, a new transgenic model is developed in which β-cells are nearly completely ablated in mice. If given insulin, these mice survive, and grow new β-cells. Lineage-tracing shows that these new β-cells come from α-cells, revealing a previously disregarded degree of pancreatic cell plasticity.
Cited By21
Newest
Published on Apr 5, 2019in Seminars in Immunopathology6.80
Elise Dalmas (Paris Diderot University)
Growing evidence suggests that components of the innate immune system play a crucial role in regulating metabolic homeostasis. Macrophages were the primary immune cells to be described in both the white adipose tissue and the pancreatic islets. Therein, their functions, beneficial or detrimental, are extending under steady state and in the context of obesity-induced type 2 diabetes. Other populations, including innate lymphoid cells, are emerging as key sentinels of metabolic tissues and privile...
Published on Apr 24, 2019in Experimental Diabetes Research
Satoshi Okano6
Estimated H-index: 6
(YU: Yamagata University),
Akira Yasui57
Estimated H-index: 57
(Tohoku University)
+ 3 AuthorsOsamu Nakajima24
Estimated H-index: 24
(YU: Yamagata University)
Our earlier studies demonstrated that cysteine414- (zinc-binding site of mCRY1-) alanine mutant mCRY1 transgenic mice (Tg mice) exhibit diabetes characterized by the reduction of β-cell proliferation and by β-cell dysfunction, presumably caused by senescence-associated secretory phenotype- (SASP-) like characters of islets. Earlier studies also showed that atypical duct-like structures in the pancreas developed age-dependently in Tg mice. Numerous reports have described that karyopherin alpha 2 ...
Published on Mar 21, 2019in bioRxiv
Manesh Chittezhath (NTU: Nanyang Technological University), Divya Gunaseelan (NTU: Nanyang Technological University)+ 9 AuthorsStefan Bornstein (NTU: Nanyang Technological University)
{beta}-cells respond to peripheral insulin resistance by increasing circulating insulin in early type-2 diabetes (T2D). Islet remodeling supports this compensation but the drivers of this process remain poorly understood. Infiltrating macrophages have been implicated in late stage T2D but relatively little is known on islet resident macrophages, especially in early T2D. We hypothesize that islet resident macrophages contribute to islet vascular remodeling and hyperinsulinemia, the failure of whi...
Published on Feb 1, 2019in Journal of Endocrinology4.38
Jose Casasnovas1
Estimated H-index: 1
(IU: Indiana University),
Yunhee Jo (IU: Indiana University)+ 3 AuthorsKok Lim Kua (IU: Indiana University)
Published on Feb 1, 2019in Cell Metabolism22.41
Wei Ying12
Estimated H-index: 12
(UCSD: University of California, San Diego),
Yun Sok Lee27
Estimated H-index: 27
(UCSD: University of California, San Diego)
+ 11 AuthorsMatthew Riopel3
Estimated H-index: 3
(UCSD: University of California, San Diego)
Summary The nature of obesity-associated islet inflammation and its impact on β cell abnormalities remains poorly defined. Here, we explore immune cell components of islet inflammation and define their roles in regulating β cell function and proliferation. Islet inflammation in obese mice is dominated by macrophages. We identify two islet-resident macrophage populations, characterized by their anatomical distributions, distinct phenotypes, and functional properties. Obesity induces the local exp...
Published on Jan 1, 2019
Limor Landsman15
Estimated H-index: 15
(TAU: Tel Aviv University)
Glucose homeostasis relies on tightly regulated insulin secretion from pancreatic beta-cells, and its loss in diabetes is associated with the dysfunction of these cells. Beta-cells reside in the islets of Langerhans, which are highly vascularized by a dense capillary network comprised of endothelial cells and pericytes. While the requirement of the endothelium for the proper pancreatic function is well established, the role of pancreatic pericytes has only recently begun to unveil. Recent studie...
Published on Dec 1, 2018in Nature Communications11.88
Nadia Cobo-Vuilleumier10
Estimated H-index: 10
(Pablo de Olavide University),
Petra I. Lorenzo2
Estimated H-index: 2
(Pablo de Olavide University)
+ 28 AuthorsChristian Claude Lachaud6
Estimated H-index: 6
(Pablo de Olavide University)
Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreat...
Published on Nov 27, 2018in bioRxiv
Dominika Nackiewicz7
Estimated H-index: 7
(UBC: University of British Columbia),
Meixia Dan2
Estimated H-index: 2
(UBC: University of British Columbia)
+ 4 AuthorsJan A. Ehses32
Estimated H-index: 32
(UBC: University of British Columbia)
Pancreatic beta-cell death occurs in diabetes and contributes to hyperglycemia. By sampling the local tissue environment, macrophages act as critical gatekeepers of tissue homeostasis in health and disease. Here, we show that, following beta-cell death, islet macrophages acquire a state of heightened IGF-1 secretion, decreased proinflammatory cytokine expression, and transcriptome changes indicative of altered cellular metabolism. This was consistently observed across three rodent models of type...
Published on Mar 1, 2018in Journal of Cell Communication and Signaling3.69
Stephen M. Twigg43
Estimated H-index: 43
(USYD: University of Sydney)
Across the years the CCNs have been increasingly implicated in the development of obesity, diabetes and its complications. Evidence for this is currently derived from their dysregulation in key metabolic pathological states in humans, animal and in vitro models, and also pre-clinical effects of their bioactivities. CCN2 is the best studied in this disease process and the other CCNs are yet to be better defined. Key steps where CCNs may play a pathogenic metabolic role include: (i) obesity and in...
Published on Jan 1, 2018in Annals of Dermatology1.65
Kunihiro Hayakawa4
Estimated H-index: 4
(Juntendo University),
Keigo Ikeda12
Estimated H-index: 12
(Juntendo University)
+ 9 AuthorsKenji Takamori35
Estimated H-index: 35
(Juntendo University)