Loss of PKGIβ/IRAG1 Signaling Causes Anemia-Associated Splenomegaly

Majer, Michael; Prueschenk, Sally; Schlossmann, Jens

doi:10.3390/ijms22115458

Cited by 4 publications

(7 citation statements)

References 41 publications

(115 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was likely the cause of severe anemia in the patient 3 years prior to the study, or anemia was the cause of splenomegaly. [ 15 ] It was also considered that the abnormally proliferating accessory spleen compressed the branches of the splenic vein, which could have caused the dilation and rupture of veins in the gastric fundus. After the accessory spleen enlarged further, its demand for blood supply increased, and, at the same time, the blood vessels entering and leaving the accessory spleen became enlarged.…”

Section: Discussionmentioning

confidence: 99%

Rare case of upper gastrointestinal hemorrhage due to accessory spleen: A case report

et al. 2022

View full text Add to dashboard Cite

Rationale: Upper gastrointestinal hemorrhage (UGIH) is defined as hemorrhage originating from the gastrointestinal tract proximal to the ligament of Treitz. The causes of UGIH include esophagitis, gastritis, peptic ulcers, Mallory-Weiss syndrome, and cancer. However, a rare cause of UGIH, such as an accessory spleen, may lead to serious complications if left untreated and can sometimes be very difficult to diagnose preoperatively.Patient concerns: An 18-year-old man was admitted to the Department of Gastroenterology of our hospital due to "repeated black stool for 2 months with aggravation, accompanied by hematemesis for 9 days." He denied any history of hepatitis, trauma, or surgery.Diagnosis: Laboratory evaluation revealed severe anemia (hemoglobin, 6.4 g/dL). Computed tomography revealed a mass measuring 127 mm in its largest dimension, located in the upper left abdomen, with varicose veins in the gastric fundus. Moreover, distended blue-purple tortuous veins were observed by gastroscopy in the gastric fundus. We believed the mass was likely an abnormally proliferating accessory spleen; however, the causes of severe anemia and gastrointestinal hemorrhage were unknown.Interventions: After discussion in a multidisciplinary conference, the mass was completely resected laparoscopically, and the subserosal veins in the gastric fundus were sutured using absorbable threads.Outcomes: After the surgery, the patient recovered uneventfully without any complications. Clinicopathological examination showed that the mass was chronic congestive splenomegaly. Gastrointestinal hemorrhage secondary to an abnormally proliferating accessory spleen was confirmed as the diagnosis. Laboratory evaluation revealed hemoglobin at 12.1 g/dL 2 months after surgery. At the 12-month follow-up, the patient showed no recurrence of gastrointestinal hemorrhage.Lessons: UGIH caused by accessory spleen is extremely rare. This entity should be considered in differential diagnosis of gastrointestinal hemorrhage. Surgical intervention is necessary for timely diagnosis and treatment in case of gastrointestinal hemorrhage in critical clinical situations.

show abstract

Section: Discussionmentioning

confidence: 99%

Rare case of upper gastrointestinal hemorrhage due to accessory spleen: A case report

et al. 2022

View full text Add to dashboard Cite

show abstract

“…This translocation could not be observed in vascular smooth muscle cells (VSMCs) of global Irag1 -deficient mice [ 4 ]. However, the loss of the interaction between IRAG1 and PKGIβ may be the reason why protein expression of PKGIβ is reduced in Irag1 mouse mutants [ 3 , 4 , 16 , 17 ]. In contrast, the coiled-coil domain of IRAG1 is not involved in any interaction between IRAG1 and PKGIβ, but is necessary for the interaction of IRAG1 with the IP 3 R-I [ 1 ].…”

Section: Functional Features Of Irag1mentioning

confidence: 99%

“…These pathological changes could also be observed in global Irag1 -/- mice [ 4 ]. Further studies with these transgenic mice revealed that they had iron deficiency anemia as a result of gastrointestinal bleeding and subsequently developed splenomegaly [ 16 ]. The results verified indications of splenomegaly in earlier studies of Irag1 mouse mutants [ 3 , 4 ].…”

Section: Functional Features Of Irag1mentioning

confidence: 99%

See 1 more Smart Citation

Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2

Prüschenk

Majer

Schlossmann

2023

IJMS

Self Cite

View full text Add to dashboard Cite

The inositol triphosphate-associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins that regulate intracellular Ca2+. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca2+ channel IP3R-I and the PKGIβ and inhibits IP3R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homolog of IRAG1 and was recently also determined as a PKGI substrate. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile elucidated in a variety of human and murine tissues, e.g., of IRAG1 in various smooth muscles, heart, platelets, and other blood cells, of IRAG2 in the pancreas, heart, platelets, and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g., smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these two regulatory proteins to envision their molecular and (patho-)physiological tasks and to unravel their functional interplay as possible (patho-)physiological counterparts.

show abstract

“…This is accompanied by downregulation of the specific β-isoform of PKGI (PKGIβ) protein. This leads to the hypothesis, that a loss of PKGIβ/IRAG1 signaling causes these physiological defects [ 8 ].…”

Section: Communicationmentioning

confidence: 99%