Analysis of heat shock protein 70 gene polymorphisms Mexican patients with idiopathic pulmonary fibrosis

Aquino‐Gálvez, Arnoldo; González-Ávila, Georgina; Pérez-Rodríguez, Martha; Partida-Rodríguez, Oswaldo; Nieves-Ramı́rez, Miriam; Piña-Ramírez, Inocencio; Ramírez-Martínez, Gustavo; Castillejos-López, Manuel; Checa, Marco; Ruiz, Vı́ctor; Urrea, Francisco; Sommer, Bettina; Zúñiga, Joaquı́n; Selman, Moisés

doi:10.1186/s12890-015-0127-7

Cited by 21 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Single nucleotide polymorphisms (SNPs) may be associated with changes in gene expression, affect gene product and thus contribute to susceptibility to disease. HSP70 polymorphisms have been found to be related to various diseases such as pulmonary fibrosis [18,19], atherosclerosis [20], coronary heart disease [21] and COPD [13]. Furthermore, the HSP70 rs1061581 variant was associated with COPD in the Croatian population [22].…”

Section: Introductionmentioning

confidence: 99%

Increased HSP70 and TLR2 Gene Expression and Association of HSP70 rs6457452 Single Nucleotide Polymorphism with the Risk of Chronic Obstructive Pulmonary Disease in the Croatian Population

et al. 2021

View full text Add to dashboard Cite

Heat shock protein 70 (Hsp70) engages Toll-like receptors (TLR) 2 and 4 when found in the extracellular compartment and contributes to inflammation in chronic obstructive pulmonary disease (COPD). Since there is growing evidence for the genetic risk factors for COPD, the gene expression of HSP70, TLR2 and TLR4 was determined, as well as the association between HSP70, TLR2 and TLR4 single nucleotide polymorphisms, (SNPs) and COPD. The gene expression was assessed in peripheral blood cells of 137 COPD patients and 95 controls by a quantitative polymerase chain reaction (qPCR), while a total of nine SNPs were genotyped by TaqMan allelic discrimination real-time PCR. HSP70 and TLR2 gene expression was increased in COPD patients compared to the controls, regardless of the disease severity and smoking status of participants. The rs6457452 SNP of HSP70 was associated with COPD, indicating the protective role of the T allele (OR = 0.46, 95% CI = 0.24–0.89, p = 0.022). Furthermore, COPD C/T heterozygotes showed a decreased HSP70 mRNA level compared to COPD C/C homozygotes. In conclusion, HSP70 and TLR2 may have a role in the pathogenesis of COPD, and the HSP70 rs6457452 variant might influence the genetic susceptibility to COPD in the Croatian population.

show abstract

Section: Introductionmentioning

confidence: 99%

Increased HSP70 and TLR2 Gene Expression and Association of HSP70 rs6457452 Single Nucleotide Polymorphism with the Risk of Chronic Obstructive Pulmonary Disease in the Croatian Population

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, studies of Hsp70 in human IPF are scarce. Circulating autoantibodies to Hsp70 have been reported in association with worse outcome among individuals with IPF (14), and analysis of Hsp70 gene polymorphisms in a cohort of Mexican patients with IPF demonstrated that some of these polymorphisms are associated with a decreased risk of IPF (15). These are intriguing observations; however, these studies did not specifically investigate the role of Hsp70 in the pathogenesis of human IPF.…”

mentioning

confidence: 98%

Intracellular Heat Shock Protein 70 Deficiency in Pulmonary Fibrosis

Sellarés

Veraldi

Thiel

et al. 2019

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) pathogenesis has been postulated to involve a variety of mechanisms associated with the aging process, including loss of protein homeostasis (proteostasis). Heat shock proteins are cellular chaperones that serve a number of vital maintenance and repair functions, including the regulation of proteostasis. Previously published data have implicated heat shock protein 70 (Hsp70) in the development of pulmonary fibrosis in animal models. We sought to identify alterations in Hsp70 expression in IPF lung. Hsp70 mRNA and protein were decreased in primary fibroblasts cultured from IPF versus normal donor lung tissue. In addition to cultured fibroblasts, Hsp70 expression was decreased in intact IPF lung, a stressed environment in which upregulation of protective heat shock proteins would be anticipated. In support of a mechanistic association between decreased Hsp70 and fibrosis, cultured primary lung fibroblasts deficient in Hsp70 secreted increased extracellular matrix proteins. Treatment of primary normal human lung fibroblasts in vitro with either of the profibrotic molecules IGFBP5 (insulin-like growth factor-binding protein 5) or transforming growth factor-b1 downregulated Hsp70, suggesting Hsp70 is a downstream target in the fibrotic cascade. Hsp70-knockout mice subjected to an inhalational bleomycin model of pulmonary fibrosis demonstrated accelerated fibrosis versus wild-type control animals. We therefore conclude that reduced Hsp70 protein contributes to fibrosis and that interventions aimed at restoring normal expression of Hsp70 represent a novel therapeutic strategy for pulmonary fibrosis.

show abstract

“…For example, it is known that production of some chaperone proteins declines with age in many tissues, suggesting that nonspecific hydrophobic interactions might be more likely to occur under these scenarios. Consistent with this, levels of the chaperone protein HSP70 have recently been shown to be reduced in the lungs of patients with IPF (23). Alternatively, one other potential mechanism by which aging might contribute to protein accumulation is through a decline in metabolic health of AEII cells.…”

Section: The Alveolar Epithelium In Ipf Is a Challenging Environment mentioning

confidence: 67%

Protein Folding and the Challenges of Maintaining Endoplasmic Reticulum Proteostasis in Idiopathic Pulmonary Fibrosis

Romero

Summer

2017

Annals ATS

View full text Add to dashboard Cite

Alveolar epithelial type II (AEII) cells are "professional" secretory cells that synthesize and secrete massive quantities of proteins to produce pulmonary surfactant and maintain airway immune defenses. To facilitate this high level of protein synthesis, AEII cells are equipped with an elaborate endoplasmic reticulum (ER) structure and possess an abundance of the machinery needed to fold, assemble, and secrete proteins. However, conditions that suddenly increase the quantity of new proteins entering the ER or that impede the capacity of the ER to fold proteins can cause misfolded or unfolded proteins to accumulate in the ER lumen, also called ER stress. To minimize this stress, AEII cells adapt by (1) reducing the quantity of proteins entering the ER, (2) increasing the amount of protein-folding machinery, and (3) removing misfolded proteins when they accumulate. Although these adaptive responses, aptly named the unfolded protein response, are usually effective in reducing ER stress, chronic aggregation of misfolded proteins is recognized as a hallmark feature of AEII cells in patients with idiopathic pulmonary fibrosis (IPF). Although mutations in surfactant proteins are linked to the development of ER stress in some rare IPF cases, the mechanisms causing protein misfolding in most cases are unknown. In this article, we review the mechanisms regulating ER proteostasis and highlight specific aspects of protein folding and the unfolded protein response that are most vulnerable to failure. Then, we postulate mechanisms other than genetic mutations that might contribute to protein aggregation in the alveolar epithelium of IPF lung.

show abstract

Analysis of heat shock protein 70 gene polymorphisms Mexican patients with idiopathic pulmonary fibrosis

Cited by 21 publications

References 48 publications

Increased HSP70 and TLR2 Gene Expression and Association of HSP70 rs6457452 Single Nucleotide Polymorphism with the Risk of Chronic Obstructive Pulmonary Disease in the Croatian Population

Increased HSP70 and TLR2 Gene Expression and Association of HSP70 rs6457452 Single Nucleotide Polymorphism with the Risk of Chronic Obstructive Pulmonary Disease in the Croatian Population

Intracellular Heat Shock Protein 70 Deficiency in Pulmonary Fibrosis

Protein Folding and the Challenges of Maintaining Endoplasmic Reticulum Proteostasis in Idiopathic Pulmonary Fibrosis

Contact Info

Product

Resources

About