FIbrosis ///////Unifying mechanism for different fibrotic diseases. Wernig G et al. (2017) Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun-mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions.//////////////////
CD47 or Integrin-associated protein (IAP) is a 50-kD membrane protein with an amino-terminal immunoglobulin domain and a carboxyl-terminal multiply membrane-spanning region. It is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. IAP is also expressed on erythrocytes, which have no known integrins. IAP is identical to OA3, an ovarian carcinoma antigen (Mawby et al., 1994). By expression studies on human erythrocytes and IAP transfectants, IAP was shown to be identical to the 1D8 antigen and to CD47, a cell surface protein with broad tissue distribution.
NCBI Summary:
This gene encodes a membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. The encoded protein is also a receptor for the C-terminal cell binding domain of thrombospondin, and it may play a role in membrane transport and signal transduction. This gene has broad tissue distribution, and is reduced in expression on Rh erythrocytes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]
General function
Receptor, Cell adhesion molecule
Comment
It was found by Brittain et al. (2001) to activate G protein signaling. Soluble thrombospondin via integrin-associated protein CD47 increases the adhesiveness of sickle red blood cells (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of CD47 and shear stress and is mediated by the activation of large G proteins and tyrosine kinases.
Cellular localization
Plasma membrane
Comment
Ovarian function
Follicle development, Luteinization
Comment
Expression regulated by
LH
Comment
Ovarian localization
Granulosa, Luteal cells
Comment
Expression and localization of members of the thrombospondin family during final follicle maturation and corpus luteum formation and function in the bovine ovary. Berisha B et al. (2016) The aim of this study was to characterize the expression patterns and localization of the thrombospondin family members (THBS1, THBS2) and their receptors (CD36 and CD47) in bovine ovaries. First, the antral follicles were classified into 5 groups based on the follicle size and estradiol-17beta (E2) concentration in the follicular fluid (< 0.5, 0.5-5, 5-40, 40-180 and > 180 E2 ng/ml). Second, the corpus luteum (CL) was assigned to the following stages: days 1-2, 3-4, 5-7, 8-12, 13-16, and > 18 of the estrous cycle and of pregnancy (month 1-2, 3-4, 6-7, > 8). Third, the corpora lutea were collected by transvaginal ovariectomy before and 0.5, 2, 4, 12, 24, 48 and 64 h after inducing luteolysis by injecting a prostaglandin F2alpha analog. The mRNA expression of examined factors was measured by RT-qPCR, steroid hormone concentration by EIA, and localization by immunohistochemistry. The mRNA expression of THBS1, THBS2, CD36, and CD47 in the granulosa cells and theca interna was high in the small follicles and reduced in the preovulatory follicles. The mRNA expression of THBS1, THBS2, and CD47 in the CL during the estrous cycle was high, but decreased significantly during pregnancy. After induced luteolysis, thrombospondins increased significantly to reach the maximum level at 12 h for THBS1, 24 h for THBS2, and 48 h for CD36. The temporal expression and localization pattern of the thrombospondins and their specific receptors in the antral follicles and corpora lutea during the different physiological phases of the estrous cycle and induced luteolysis appear to be compatible with their inhibitory role in the control of ovarian angiogenesis.//////////////////
Higuchi et al. (1999) raised a monoclonal antibody (mAb) designated OG-4 against human granulosa cells (GC). By immunohistochemistry, the expression of OG-4 antigen was observed on human GC and large luteal cells, but not on thecal and small luteal cells. A complementary DNA (cDNA) clone encoding OG-4 antigen was screened and isolated by a panning method using OG-4 mAb from a human corpus luteum (GL) cDNA library that was expressed transiently in COS-7 cells, Nucleotide sequencing revealed that OG-4 antigen was identical to integrin-associated protein (IAP)/CD47 antigen. Subsequent reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the isoform 2 mRNA of IAP is predominantly expressed in human GC and CL. Furthermore, TSP-1, which is a ligand for CD47, is expressed in human granulosa cell as shown by immunocytochemistry and RT-PCR. Co-expresson of CD47 and TSP-1 on human GC may suggest that TSP-1 has a physiological role in GC function possibly via CD47 in an autocrine fashion.
Follicle stages
Preovulatory
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Lindberg et al. (1996) reported decreased resistance to bacterial infection and granulocyte defects in IAP/CD47-deficient knock out mice.