Integrin α1-null Mice Exhibit Improved Fatty Liver When Fed a High Fat Diet Despite Severe Hepatic Insulin Resistance

Williams, Ashley S.; Li, Kang; Zheng, Jiangxia; Grueter, Carrie A.; Bracy, Deanna P.; James, Freyja D.; Pozzi, Ambra; Wasserman, David H.

doi:10.1074/jbc.m114.615716

Cited by 42 publications

(35 citation statements)

References 57 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacological progress in blocking integrin α1 on human immune cells to reduce inflammation has, nevertheless, been slow, although anti-VLA-1 antibody treatment has been suggested to be beneficial to treat inflammatory conditions, such as rheumatoid arthritis and psoriasis, that involve localized pathological memory T-cells, (Gardner, 2014). A role for α1β1 in liver has recently been discovered, almost 20 years after the original integrin α1 −/− mouse strain was created, and recent data show that severity of obesity-induced fatty liver disease is attenuated in integrin α1 −/− mice (Williams et al, 2015). Although α1β1 is the only collagen receptor on hepatocytes (Gullberg et al, 1990), it does not seem to be involved in liver fibrosis.…”

Section: α10β1mentioning

confidence: 99%

The integrin–collagen connection – a glue for tissue repair?

Zeltz

Gullberg

2016

Journal of Cell Science

176

126

View full text Add to dashboard Cite

There was an error published in J. Cell Sci. 129, 653-664.In Fig. 2A, the fibroblasts were incorrectly labelled. The correct annotation should have been α11 −/− fibroblast (left) and α11 +/+ fibroblast (right). The correct Fig. 2 is shown below. We apologise to the readers for any confusion that this error might have caused. Journal of Cell Science COMMENTARYThe integrin-collagen connection -a glue for tissue repair?Cedric Zeltz and Donald Gullberg* ABSTRACTThe α1β1, α2β1, α10β1 and α11β1 integrins constitute a subset of the integrin family with affinity for GFOGER-like sequences in collagens.Integrins α1β1 and α2β1 were originally identified on a subset of activated T-cells, and have since been found to be expressed on a number of cell types including platelets (α2β1), vascular cells (α1β1, α2β1), epithelial cells (α1β1, α2β1) and fibroblasts (α1β1, α2β1).Integrin α10β1 shows a distribution that is restricted to mesenchymal stem cells and chondrocytes, whereas integrin α11β1 appears restricted to mesenchymal stem cells and subsets of fibroblasts. The bulk of the current literature suggests that collagen-binding integrins only have a limited role in adult connective tissue homeostasis, partly due to a limited availability of cell-binding sites in the mature fibrillar collagen matrices. However, some recent data suggest that, instead, they are more crucial for dynamic connective tissue remodeling events -such as wound healing -where they might act specifically to remodel and restore the tissue architecture. This Commentary discusses the recent development in the field of collagen-binding integrins, their roles in physiological and pathological settings with special emphasis on wound healing, fibrosis and tumor-stroma interactions, and include a discussion of the most recently identified newcomers to this subfamilyintegrins α10β1 and α11β1.

show abstract

Section: α10β1mentioning

confidence: 99%

The integrin–collagen connection – a glue for tissue repair?

Zeltz

Gullberg

2016

Journal of Cell Science

176

126

View full text Add to dashboard Cite

show abstract

“…In one study, tail-vein injection of HFD-fed mice with a hydrolase for hyaluronan, an ECM component, reduces features of muscle and liver insulin resistance (Kang et al, 2013). Moreover, integrin-α1-subunit-deficient mice ( Itga1 −/− ) fed an HFD display reduced fatty liver content but also severe hepatic insulin resistance, compared to wild-type HFD-fed controls (Williams et al, 2015b). …”

Section: Discussionmentioning

confidence: 99%

Hepatic Dysfunction Caused by Consumption of a High-Fat Diet

Soltis

Kennedy

et al. 2017

Cell Reports

View full text Add to dashboard Cite

SUMMARY Obesity is a major human health crisis that promotes insulin resistance and, ultimately, type 2 diabetes. The molecular mechanisms that mediate this response occur across many highly complex biological regulatory levels that are incompletely understood. Here, we present a comprehensive molecular systems biology study of hepatic responses to high-fat feeding in mice. We interrogated diet-induced epigenomic, transcriptomic, proteomic, and metabolomic alterations using high-throughput omic methods and used a network modeling approach to integrate these diverse molecular signals. Our model indicated that disruption of hepatic architecture and enhanced hepatocyte apoptosis are among the numerous biological processes that contribute to early liver dysfunction and low-grade inflammation during the development of diet-induced metabolic syndrome. We validated these model findings with additional experiments on mouse liver sections. In total, we present an integrative systems biology study of diet-induced hepatic insulin resistance that uncovered molecular features promoting the development and maintenance of metabolic disease.

show abstract

“…Physiological, integrinmediated cell-ECM communication is critical not only normal ␤-cell function and indeed survival, as discussed here, but also for insulin action on its target tissues. Pathological modification of the ECM in type 2 diabetes, for example by high-fat diet, hyperglycemia-induced advanced glycation end-products (AGEs), or inflammatory cytokine-induced fibrosis, has thus been shown to participate in the insulin resistance state of insulin-targeted tissues (muscle, adipose tissue, and liver) and could impair ␤-cell function in a similar fashion (4,50,59,107,138,146,147). Deleterious cytokines that are elevated in the circulation of individuals with type 2 diabetes directly affect the expression of proteins of different functional classes including the actin cytoskeleton in ␤-cells (103); perhaps this may also occur in target cells to modulate their insulin sensitivity.…”

Section: Cytoskeleton and Fa Remodeling In Type 2 Diabetes: Parallelsmentioning

confidence: 98%

The skeleton in the closet: actin cytoskeletal remodeling in β-cell function

Arous

Halban

2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Over the last few decades, biomedical research has considered not only the function of single cells but also the importance of the physical environment within a whole tissue, including cell-cell and cell-extracellular matrix interactions. Cytoskeleton organization and focal adhesions are crucial sensors for cells that enable them to rapidly communicate with the physical extracellular environment in response to extracellular stimuli, ensuring proper function and adaptation. The involvement of the microtubular-microfilamentous cytoskeleton in secretion mechanisms was proposed almost 50 years ago, since when the evolution of ever more sensitive and sophisticated methods in microscopy and in cell and molecular biology have led us to become aware of the importance of cytoskeleton remodeling for cell shape regulation and its crucial link with signaling pathways leading to β-cell function. Emerging evidence suggests that dysfunction of cytoskeletal components or extracellular matrix modification influences a number of disorders through potential actin cytoskeleton disruption that could be involved in the initiation of multiple cellular functions. Perturbation of β-cell actin cytoskeleton remodeling could arise secondarily to islet inflammation and fibrosis, possibly accounting in part for impaired β-cell function in type 2 diabetes. This review focuses on the role of actin remodeling in insulin secretion mechanisms and its close relationship with focal adhesions and myosin II.

show abstract

Integrin α1-null Mice Exhibit Improved Fatty Liver When Fed a High Fat Diet Despite Severe Hepatic Insulin Resistance

Cited by 42 publications

References 57 publications

The integrin–collagen connection – a glue for tissue repair?

The integrin–collagen connection – a glue for tissue repair?

Hepatic Dysfunction Caused by Consumption of a High-Fat Diet

The skeleton in the closet: actin cytoskeletal remodeling in β-cell function

Contact Info

Product

Resources

About