Last update 19 Sep 2024

SPTBN1

Last update 19 Sep 2024

Basic Info

Synonyms

Beta-II spectrin, Fodrin beta chain, Spectrin beta chain, non-erythrocytic 1

+ [4]

Introduction

Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function.

Drugs associated with SPTBN1

BF-114

Target

SPTBN1

Mechanism

SPTBN1 inhibitors

Active Org.

Bullfrog International LC [+1]

Originator Org.

Bullfrog International LC

Active Indication

Hepatocellular Carcinoma [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SPTBN1

100 Translational Medicine associated with SPTBN1

0 Patents (Medical) associated with SPTBN1

202

Literatures (Medical) associated with SPTBN1

01 Sep 2024·Cell Reports

Aldehydes alter TGF-β signaling and induce obesity and cancer

Article

Author: Merrill, Joseph R. ; Crawford, James M. ; Rao, Shuyun ; Wang, Xin Wei ; Crandall, Keith ; Latham, Patricia S ; Mishra, Lopa ; Ohshiro, Kazufumi ; Amdur, Richard L. ; Krainer, Adrian R. ; Xiang, Xiyan ; Hassan, Md. Imtaiyaz ; Shetty, Kirti ; Mohammad, Taj ; John, Sahara ; Amdur, Richard L ; Mishra, Bibhuti ; Bhowmick, Krishanu ; Latham, Patricia S. ; Lyons, Scott K. ; Wang, Zhanwei ; Hassan, Md Imtaiyaz ; Merrill, Joseph R ; Dasarathy, Srinivasan ; Yang, Xiaochun ; Krainer, Adrian R ; Yu, Herbert ; Huang, Hai ; Cifani, Paolo ; Crawford, James M ; Vegesna, Anil K ; Vegesna, Anil K. ; Lyons, Scott K

Obesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)-affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2^-/- and Aldh2^-/-Sptbn1^+/- mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). Mechanistic studies demonstrate aberrant transforming growth factor β (TGF-β) signaling through 4-HNE modification of the SMAD3 adaptor SPTBN1 (β2-spectrin) to pro-fibrotic and pro-oncogenic phenotypes, which is restored to normal SMAD3 signaling by targeting SPTBN1 with small interfering RNA (siRNA). Significantly, therapeutic inhibition of SPTBN1 blocks MASH and fibrosis in a human model and, additionally, improves glucose handling in Aldh2^-/- and Aldh2^-/-Sptbn1^+/- mice. This study identifies SPTBN1 as a critical regulator of the functional phenotype of toxic aldehyde-induced MASH and a potential therapeutic target.

01 Jul 2024·Neuroscience

GM1 Ameliorates Neuronal Injury in Rats after Cerebral Ischemia and Reperfusion: Potential Contribution of Effects on SPTBN1-mediated Signaling

Article

Author: Sun, Chun-Yan ; Liu, Jia-Xing ; Wang, Cai-Ping ; Shi, Yun-Wei ; Liu, Dong ; Zhao, Shu-Yong ; Fan, Xing-Juan ; Xu, Chun-Cheng

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg^-1·d^-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 μM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.

01 Jan 2024·Journal of Cellular Physiology

Tumor cell SPTBN1 inhibits M2 polarization of macrophages by suppressing CXCL1 expression

Article

Author: Yao, Liangqing ; Meng, Dan ; Wang, Xinhong ; Jin, Quanshan ; Wu, Huijie ; Jiang, Nan ; Jin, Jiayu ; Li, Jiajia ; Wei, Xiangxiang ; Zhi, Xiuling ; Guo, Jieyu

AbstractTumor‐associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2‐type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non‐erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/− mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid‐derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription–quantitative real‐time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA‐MB‐231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA‐MB‐231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic‐nuclear protein isolation experiments and ChIP‐qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2‐type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

SPTBN1

Basic Info

Related

Analysis