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C1QTNF5

Official Full Name
C1q and tumor necrosis factor related protein 5
Background
This gene encodes a member of the a member of the C1q/tumor necrosis factor superfamily. The encoded protein may be a component of basement membranes and may play a role in cell adhesion. This gene is contained entirely within the 3' UTR of the membrane frizzled-related protein gene on chromosome 11q23 and both genes are expressed from a bicistronic transcript. Mutations in this gene have been associated with late-onset retinal degeneration.
Synonyms
C1q and tumor necrosis factor related protein 5; C1QTNF5; Complement C1q tumor necrosis factor related protein 5 precursor; LORD; CTRP5; DKFZp586B0621; FLJ30570; wu:fb02c10; wu:fb02f05; zgc:112378; complement C1q tumor necrosis factor-related protein 5

Recent Research Progress

C1q tumor necrosis factor alpha-related protein isoform 5 (CTRP5, also known as C1QTNF5), a new member of the secreted protein family, was recently identified as a novel, highly conserved adiponectin paralog family, and its biological function is similar to that of myocyte adiponectin. Adiponectin is a rich adipokines mainly secreted from adipose tissue and is involved in the regulation of energy metabolism, such as fatty acid and glucose oxidation. Recently, it has been reported that CTRP5 is associated with various diseases.

New pathogenic mutations in CTRP5 support dominant negative disease mechanisms in late-onset retinal degeneration

Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy, characterized by extensive sub-retinal pigment epithelial (RPE) deposition, RPE atrophy, choroidal neovascularization, and severe vision Loss of associated photoreceptor cell death. L-ORD shows a striking phenotypic similarity to age-related macular degeneration (AMD), a common hereditary complex disease that can lead to early misdiagnosis. To date, a single missense mutation (S163R) in the CTRP5 gene has been shown to cause L-ORD in a subset of affected families. Three new pathogenic mutations in CTRP5 have recently been identified and characterized to elucidate disease mechanisms. In silico and in vitro characterization revealed that these mutations disrupt the folding, assembly or polarity of proteins secreted by CTRP5 and, importantly, all of these mutations appear to destabilize wild-type proteins in co-transfection experiments with human RPE cell lines. This suggests that heterozygous mutations in L-ORD show a dominant negative, rather than a disease mechanism of haploid deficiency. The function of CTRP5 remains unclear, but this new insight into the pathogenic basis of L-ORD has implications for future therapeutic strategies such as gene-enhanced therapies.

CTRP5 improves palmitic acid-induced apoptosis and insulin resistance by activating AMPK and fatty acid oxidation

Lipid toxicity caused by high concentrations of saturated fatty acids is closely related to the development of insulin resistance and skeletal muscle cell apoptosis. CTRP5 is known to activate AMP-activated protein kinase (AMPK) and fatty acid oxidation; however, the effect of CTRP5 on palmitic acid-induced lipotoxicity in myocyte has not been studied. Recent studies have found that the globular domain of CTRP5 (gCTRP5) prevents palmitic acid-induced myocyte apoptosis and insulin resistance by inhibiting the activation of caspase-3, reactive oxygen species accumulation, and IRS-1 reduction. These beneficial effects of gCTRP5 are primarily attributable to an increase in fatty acid oxidation by phosphorylation of AMPK. These results provide a new function of CTRP5, which may have potential for prevention and treatment in the management of obesity, insulin resistance and type 2 diabetes mellitus.

CTRP5 as a potential novel inflammatory biomarker for chronic obstructive pulmonary disease

Local and systemic inflammation is commonly found in chronic obstructive pulmonary disease (COPD). Adipokines, a secretory protein mediator of adipose tissue, have been found to be involved in the inflammatory response in many chronic inflammatory diseases. Recent studies have shown a possible association between CTRP5 and lung function and other inflammatory markers in patients with COPD. Serum CTRP5 was significantly elevated in patients with COPD and was inversely correlated with the FEV1/FVC ratio in all patients. In patients with COPD, CTRP5 was also negatively correlated with predicted FEV 1% and positively association with CRP levels. In conclusion, circulating CTRP5 is associated with the severity of airflow obstruction and systemic inflammation in COPD patients, suggesting that it may be used as a potential novel inflammatory biomarker in COPD. Further research should be conducted to elucidate the exact role of CTRP5 in the pathogenesis and outcome of COPD.

Taken together, CTRP5 is closely related to L-ORD, obesity, type 2 diabetes mellitus and COPD. However, some related mechanisms have not been known so far. Therefore, prospective studies of CTRP5 may be helpful in assessing the clinical relevance and treatment of related diseases.

References:

  1. Stanton, et al. Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration. Scientific Reports, 2017, 7: 12147.
  2. Xia Lei, et al. Loss of CTRP5 improves insulin action and hepatic steatosis. Am J Physiol Endocrinol Metab, 2016, 310:  E1036–E1052.
  3. Yang, et al. CTRP5 ameliorates palmitate-induced apoptosis and insulin resistance through activation of AMPK and fatty acid oxidation. Biochemical and Biophysical Research Communications, 2014, 452: 715–721.
  4. Ying Shen, et al. Association of increased serum CTRP5 levels with in-stent restenosis after coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration and proliferation in vascular smooth muscle cells. International Journal of Cardiology, 2017, 228: 129–136.
  5. Xiongying Tu, et al. The macular degeneration-linked C1QTNF5 (S163) mutation causes higher-order structural rearrangements. J Struct Biol. 2014, 186(1): 86–94.
  6. Astra Dinculescu, et al. Pathological Effects of Mutant C1QTNF5 (S163R) Expression in Murine Retinal Pigment Epithelium. Inevstigative Ophthalmology & Visual Science, 2015, 56(11): 6971-6980.
  7. Diandian Li, et al. Adipokine CTRP-5 as a Potential Novel Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease. Medicine, 2015, 94(36): e1503.

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