Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases, Especially Cancer and Pregnancy Complications

Wang, Yao; Nie, Guiying

doi:10.3390/ijms221910756

Cited by 16 publications

(18 citation statements)

References 137 publications

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“…The HTRA4 gene encodes a human protease that belong to the mammalian high temperature requirement A (HtrA) family. HtrA family proteins are involved in several cellular processes, including apoptosis and unfolded protein stress response [ 33 ]. A recent study suggested that the expression of HTRA4 enhances the effect of chemotherapy in breast and lung cancer cell lines [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia

Nasimian

Ashiri

Ahmed

et al. 2023

IJMS

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Despite incredible progress in cancer treatment, therapy resistance remains the leading limiting factor for long−term survival. During drug treatment, several genes are transcriptionally upregulated to mediate drug tolerance. Using highly variable genes and pharmacogenomic data for acute myeloid leukemia (AML), we developed a drug sensitivity prediction model for the receptor tyrosine kinase inhibitor sorafenib and achieved more than 80% prediction accuracy. Furthermore, by using Shapley additive explanations for determining leading features, we identified AXL as an important feature for drug resistance. Drug−resistant patient samples displayed enrichment of protein kinase C (PKC) signaling, which was also identified in sorafenib−treated FLT3−ITD−dependent AML cell lines by a peptide−based kinase profiling assay. Finally, we show that pharmacological inhibition of tyrosine kinase activity enhances AXL expression, phosphorylation of the PKC−substrate cyclic AMP response element binding (CREB) protein, and displays synergy with AXL and PKC inhibitors. Collectively, our data suggest an involvement of AXL in tyrosine kinase inhibitor resistance and link PKC activation as a possible signaling mediator.

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Section: Resultsmentioning

confidence: 99%

A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia

Nasimian

Ashiri

Ahmed

et al. 2023

IJMS

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“…HTRA2 is an integral member of the HTRA family of serine proteases, which plays an essential role in mitochondrial homeostasis and cell apoptosis (Toyama et al, 2021; Wang & Nie, 2021; Zheng et al, 2021). Hur et al (2019) found that HTRA2 deficiency impaired mitochondrial homeostasis and promoted hepatic fibrogenesis.…”

Section: Discussionmentioning

confidence: 99%

A novel model for predicting prognosis in patients with idiopathic pulmonary fibrosis based on endoplasmic reticulum stress‐related genes

Liu,

Zhang,

Liu

et al. 2024

Cell Biology International

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Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of unknown pathogenic origin. Endoplasmic reticulum (ER) stress refers to the process by which cells take measures to ER function when the morphology and function of the reticulum are changed. Recent studies have demonstrated that the ER was involved in the evolution and progression of IPF. In this study, we obtained transcriptome data and relevant clinical information from the Gene Expression Omnibus database and conducted bioinformatics analysis. Among the 544 ER stress‐related genes (ERSRGs), 78 were identified as differentially expressed genes (DEGs). These DEGs were primarily enriched in response to ER stress, protein binding, and protein processing. Two genes (HTRA2 and KTN1) were included for constructing an accurate molecular signature. The overall survival of patients was remarkably worse in the high‐risk group than in the low‐risk group. We further analyzed the difference in immune cells between high‐risk and low‐risk groups. M0 and M2 macrophages were significantly increased in the high‐risk group. Our results suggested that ERSRGs might play a critical role in the development of IPF by regulating the immune microenvironment in the lungs, which provide new insights on predicting the prognosis of patients with IPF.

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“…Given that they are differentially expressed prior to the infection with the virulent strain, they could be promising biomarkers for recovery from virulent ASFV and increased resilience. HTRA3 is part of a highly conserved gene family of serine proteases 33 . GFTP2 controls the ux of glucose into the hexosamine pathway 34 . )…”

Section: Non-recovered Vs Recovered Contrastsmentioning

confidence: 99%

The transcriptomic insight into the differential susceptibility of African Swine Fever in inbred pigs

Banabazi,

Freimanis,

Goatley

et al. 2023

Preprint

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African swine fever (ASF) is a global threat to animal health and food security. ASF is typically controlled by strict biosecurity, rapid diagnosis and culling of affected herds. Much progress has been made in developing modified live virus vaccines against ASF. There is host variation in response to ASF infection in field and controlled conditions. To better understand the dynamics underlying this host differential morbidity, whole transcriptome profiling was carried out in twelve immunized and five sham immunized pigs. Seventeen MHC homozygous inbred Large white Babraham pigs were sampled at three time points before and after challenge. The changes in the transcriptome profiles of infected animals were surveyed over time. In addition, the immunization effect on the host response was studied as well among the contrasts of all protection subgroups. The results showed two promising candidate genes to distinguish between resilient and susceptible pigs with a virulent African swine fever virus (ASFV) pre-infection: HTRA3 and GFPT2 (padj < 0.05). Variant calling on the transcriptome assemblies showed a two-base pair insertion into the ACOX3 gene closely located to HTRA3 that may regulate its expression as a putative genomic variant for ASF. Several significant DGEs, enriched gene ontology (GO) terms, and KEGG pathways at one-day and one-week post-infection, compared to the pre-infection, indicate a significant inflammation response immediately after ASF infection. The presence of the virus was confirmed by the mapping of RNA-Seq reads on two whole viral genome sequences. This was concordant with a higher virus load in the non-recovered animals one-week post-infection. There was no transcriptome signature on the immunization at pre-infection and one-day post-infection. More samples and data from additional clinical trials may support these findings.

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Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases, Especially Cancer and Pregnancy Complications

Cited by 16 publications

References 137 publications

A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia

A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia

A novel model for predicting prognosis in patients with idiopathic pulmonary fibrosis based on endoplasmic reticulum stress‐related genes

The transcriptomic insight into the differential susceptibility of African Swine Fever in inbred pigs

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