Caveolin-1 scaffolding domain peptide regulates glucose metabolism in lung fibrosis

Gopu, Venkadesaperumal; Fan, Lei; Shetty, Rashmi S.; Nagaraja, M.R.; Shetty, Sreerama

doi:10.1172/jci.insight.137969

Cited by 28 publications

(19 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating studies have demonstrated hypoxia could significantly affect metabolic phenotype in cancer cells [ 20 , 21 ]. The association of hypoxia or HIF-α with altered metabolism in cardiovascular [ 22 , 23 ] and fibrotic disorders [ 24 ] was also reported. Many studies demonstrated that chronic hypoxia triggers signaling pathways that regulate cardiac metabolic remodeling, particularly at the transcriptional level, to maintain energy production.…”

Section: Introductionmentioning

confidence: 99%

“…He et al reported elevated HIF-1α expression and altered endothelial metabolism, including increased glycolysis and reduced oxygen consumption in the endothelium of coronary arteries after mice were treated with a PHD inhibitor, dimethyloxalylglycine. Gopu et al [ 25 ] observed increased basal expression of HIF-1α and glycolytic enzymes as well as lactate and succinate levels in fibrotic lung fibroblasts compared with normal lung fibroblasts. Keloids typically feature excessive proliferation of fibroblasts and deposition of ECM and microvascular abnormalities.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia

Wang

Qin

et al. 2021

Redox Biology

View full text Add to dashboard Cite

Keloids exhibit metabolic reprogramming including enhanced glycolysis and attenuated oxidative phosphorylation. Hypoxia induces a series of protective responses in mammalian cells. However, the metabolic phenotype of keloid fibroblasts under hypoxic conditions remains to be elucidated. The present study aimed to investigate glycolytic activity, mitochondrial function and morphology, and the HIF1α and PI3K/AKT signaling pathways in keloid fibroblasts (KFB) under hypoxic conditions. Our results showed that hypoxia promoted proliferation, migration invasion and collagen synthesis and inhibited apoptosis in KFB. The mRNA levels, protein expressions and enzyme activities of glycolytic enzymes in KFB were higher than those in normal skin fibroblasts (NFB) under normoxia. Moreover, hypoxia remarkedly upregulated glycolysis in KFB. Decreased activities of mitochondrial complexes and abnormal mitochondria were detected in KFB under normoxic conditions and the damage was aggravated by hypoxia. An intracellular metabolic profile assay suggested hypoxia increased glycolytic parameters except glycolytic reserve but inhibited the key parameters of mitochondrial function apart from H + leak. Protein levels of HIF1α and phosphorylation levels of the PI3K/AKT signaling pathway were upregulated in the context of 3% oxygen. Enhanced total reactive oxygen species (ROS), mitochondrial ROS (mitoROS) and antioxidant activities of KFB were observed in response to hypoxia. Additionally, autophagy was induced by hypoxia. Our data collectively demonstrated potentiated glycolysis and attenuated mitochondrial function under hypoxia, indicating that altered glucose metabolism regulated by hypoxia could be a therapeutic target for keloids.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia

Wang

Qin

et al. 2021

Redox Biology

View full text Add to dashboard Cite

show abstract

“…It is reported that CAV1 scaffolding domain may be critical in controlling the dynamic phenotype of cancer cells by facilitating the interaction of specific signal transduction pathways [58]. The peptide was able to competitively bind with various signal molecules and interrupt their interaction with CAV1 in vivo, exhibiting multiple biological activities [59][60][61]. The above findings suggest that the scaffolding domain might be a promising target for therapy of various diseases.…”

Section: Discussionmentioning

confidence: 89%

Reconstitution of Caveolin-1 into Artificial Lipid Membrane: Characterization by Transmission Electron Microscopy and Solid-State Nuclear Magnetic Resonance

Zhang

Kong

et al. 2021

Molecules

View full text Add to dashboard Cite

Caveolin-1 (CAV1), a membrane protein that is necessary for the formation and maintenance of caveolae, is a promising drug target for the therapy of various diseases, such as cancer, diabetes, and liver fibrosis. The biology and pathology of caveolae have been widely investigated; however, very little information about the structural features of full-length CAV1 is available, as well as its biophysical role in reshaping the cellular membrane. Here, we established a method, with high reliability and reproducibility, for the expression and purification of CAV1. Amyloid-like properties of CAV1 and its C-terminal peptide CAV1(168-178) suggest a structural basis for the short linear CAV1 assemblies that have been recently observed in caveolin polyhedral cages in Escherichia coli (E. coli). Reconstitution of CAV1 into artificial lipid membranes induces a caveolae-like membrane curvature. Structural characterization of CAV1 in the membrane by solid-state nuclear magnetic resonance (ssNMR) indicate that it is largely α-helical, with very little β-sheet content. Its scaffolding domain adopts a α-helical structure as identified by chemical shift analysis of threonine (Thr). Taken together, an in vitro model was developed for the CAV1 structural study, which will further provide meaningful evidences for the design and screening of bioactive compounds targeting CAV1.

show abstract

“…Although metabolic change is a field modestly addressed in idiopathic pulmonary fibrosis, it is involved in the survival of cells against nutrient stress, differentiation to myofibroblasts and collagen production [ 106 , 127 , 128 ]. Lactic acid, from anaerobic metabolism, has been proposed as an important mediator of myofibroblast differentiation through the pH-dependent activation of TGF-β [ 129 , 130 ]. Myofibroblasts from IPF have increased glycolysis and increased differentiation, mediated by HIF-1α and TGF-β [ 131 ].…”

Section: Hypoxia Signaling Overlap In Cancer and Fibrosis?mentioning

confidence: 99%

Hypoxia in Cancer and Fibrosis: Part of the Problem and Part of the Solution

Romero

Aquino‐Gálvez

2021

IJMS

View full text Add to dashboard Cite

Adaptive responses to hypoxia are involved in the progression of lung cancer and pulmonary fibrosis. However, it has not been pointed out that hypoxia may be the link between these diseases. As tumors or scars expand, a lack of oxygen results in the activation of the hypoxia response, promoting cell survival even during chronic conditions. The role of hypoxia-inducible factors (HIFs) as master regulators of this adaptation is crucial in both lung cancer and idiopathic pulmonary fibrosis, which have shown the active transcriptional signature of this pathway. Emerging evidence suggests that interconnected feedback loops such as metabolic changes, fibroblast differentiation or extracellular matrix remodeling contribute to HIF overactivation, making it an irreversible phenomenon. This review will focus on the role of HIF signaling and its possible overlapping in order to identify new opportunities in therapy and regeneration.

show abstract

Caveolin-1 scaffolding domain peptide regulates glucose metabolism in lung fibrosis

Cited by 28 publications

References 63 publications

Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia

Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia

Reconstitution of Caveolin-1 into Artificial Lipid Membrane: Characterization by Transmission Electron Microscopy and Solid-State Nuclear Magnetic Resonance

Hypoxia in Cancer and Fibrosis: Part of the Problem and Part of the Solution

Contact Info

Product

Resources

About