ITPR1 and Associated Diseases
With the help of our excellent and well-trained scientists, Creative Biolabs can offer a wide range of services in the field of gene therapy, especially for strategy design and function assessment of your projects. We can provide detailed and one-stop customer services to meet your requirements.
Overview of ITPR1
In humans, inositol 1,4,5-trisphosphate receptor type 1 (ITPR1, also known as InsP3R1) is an intracellular receptor encoded by ITPR1. Upon stimulated by the ligand inositol 1,4,5-trisphosphate, ITPR1 can mediate the release of calcium from the endoplasmic reticulum (ER) through the ligand-gated ion channels. ITPR1 plays an important role in ER stress-induced apoptosis. The released cytoplasmic calcium will trigger apoptosis by activation of CaM kinase II, which then results in the activation of downstream apoptosis pathways. ITPR1 also regulates the secretion of electrolytes and fluid by interacting with AHCYL1.
ITPR1 in Disease
Calcium release mediated by ITPR1 is important for a series of cellular processes. Mutations in ITPR1 are associated with diseases such as ataxia, cancer, osteoporosis, and anhidrosis.
- Osteoporosis
ITPR1 encoded InsP3R1 functions as proapoptotic mediators in the progression of osteoporosis. Dysregulated apoptosis of osteoblasts is related to prominent degenerative diseases such as osteoporosis. In bone, estrogen deficiency is a cause of accelerated osteoblast apoptosis. Etoposide is an estrogen steroid hormone. With the treatment of etoposide, G-292 human osteoblastic cells perform increased cell apoptosis and upregulated expression of caspase-3/7, which can be suppressed by the pretreatment of estradiol. Estradiol treatment inhibits the expression of proapoptotic mediator ITPR1, which means estrogens can combat osteoporosis by preventing the apoptosis caused by ITPR1.
Fig.1 Pretreatment with estradiol decreases the expression of caspase-3/7 induced by etoposide. (Bradford, 2010)
- Renal cell carcinomas
HIF2α/ITPR1 axis plays a role in regulating the cell survival of renal cell carcinomas (RCC). Inactivation of von Hippel-Lindau (VHL) gene and upregulation of hypoxia-inducible factors (HIF) are typical characteristics of RCC. Compared to the wild-type RCC cell line, one with the mutation of VHL is resistant to NK cell-mediated lysis. This resistance requires HIF2α stabilization. ITPR1 is one direct target gene of HIF2α, the knockdown of HIF2α also decreases the expression of ITPR1 in both mRNA and protein levels. Knockdown of ITPR1 will inhibit NK cell-mediated autophagy in the RCC cell line with VHL mutation. Based on this, HIF2α-dependent expression of ITPR1 can regulate the cell susceptibility of RCC to NK cell-mediated lysis.
Creative Biolabs believes in the spirit of non-stop exploration and is always ready to collaborate with our clients to provide detailed gene therapy development services with the help of our excellent and well-trained scientists. Please feel free to contact us for more about your ITPR1 project.
References
- Bradford, P. G.; et al. Estrogen regulation of apoptosis in osteoblasts. Physiology & Behavior. 2010, 99: 181–185.
- Messai, Y.; et al. ITPR1 Protects Renal Cancer Cells against Natural Killer Cells by Inducing Autophagy. Cancer Research. 2014, 74: 6820–6832.
