The regulation of CD47-SIRPα signaling axis by microRNAs in combination with conventional cytotoxic drugs together with the help of nano-delivery: a choice for therapy?

Beizavi, Zahra; Gheibihayat, Seyed Mohammad; Moghadasian, Hadis; Zare, Hossein; Yeganeh, Babak Shirazi; Askari, Hasan; Vakili, Sina; Tajbakhsh, Amir; Savardashtaki, Amir

doi:10.1007/s11033-021-06547-y

Cited by 12 publications

(5 citation statements)

References 87 publications

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“…CD47 (integrin‐associated protein, IAP) is a multifunctional cellular protein that is a significant checkpoint for regulating macrophages and DCs in the innate immune response. Many studies have revealed that cancer cells evade the immune response by increasing the expression of CD47 23,179,180 . The vital function of CD47‐SIRPα signaling in preventing phagocytosis of macrophages was demonstrated in CD47 knockout mouse models where hematopoietic cells from the CD47 knockout mice were quickly eliminated from the blood circulation by macrophages of allogenic wild‐type mouse models 181–183 .…”

Section: Tolerance and Efferocytosis Or How Apoptotic Cells Direct Im...mentioning

confidence: 99%

“…Many studies have revealed that cancer cells evade the immune response by increasing the expression of CD47. 23,179,180 The vital function of CD47-SIRPα signaling in preventing phagocytosis of macrophages was demonstrated in CD47 knockout mouse models where hematopoietic cells from the CD47 knockout mice were quickly eliminated from the blood circulation by macrophages of allogenic wild-type mouse models. [181][182][183] Pengam et al showed that the SIRPα-CD47 axis modulates chemokine release of myeloid-derived suppressor cells (MDSCs), a heterogeneous group of embryonic hematopoietic progenitors that repress immune reactions, and led to the stimulation and preservation of acquired immune tolerance to kidney allografts.…”

Section: The Regulation Of Cd47 In Transplantationmentioning

confidence: 99%

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The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles

Vafadar,

Vosough,

Jahromi

et al. 2023

Cell Biochemistry & Function

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Recently, efforts have been made to recognize the precise reason(s) for transplant failure and the process of rejection utilizing the molecular signature. Most transplant recipients do not appreciate the unknown length of survival of allogeneic grafts with the existing standard of care. Two noteworthy immunological pathways occur during allogeneic transplant rejection. A nonspecific innate immune response predominates in the early stages of the immune reaction, and allogeneic antigens initiate a donor‐specific adaptive reaction. Though the adaptive response is the major cause of allograft rejection, earlier pro‐inflammatory responses that are part of the innate immune response are also regarded as significant in graft loss. The onset of the innate and adaptive immune response causes chronic and acute transplant rejection. Currently employed immunosuppressive medications have shown little or no influence on chronic rejection and, as a result, on overall long‐term transplant survival. Furthermore, long‐term pharmaceutical immunosuppression is associated with side effects, toxicity, and an increased risk of developing diseases, both infectious and metabolic. As a result, there is a need for the development of innovative donor‐specific immunosuppressive medications to regulate the allorecognition pathways that induce graft loss and to reduce the side effects of immunosuppression. Efferocytosis is an immunomodulatory mechanism with fast and efficient clearance of apoptotic cells (ACs). As such, AC therapy strategies have been suggested to limit transplant‐related sequelae. Efferocytosis‐based medicines/treatments can also decrease the use of immunosuppressive drugs and have no detrimental side effects. Thus, this review aims to investigate the impact of efferocytosis on transplant rejection/tolerance and identify approaches using AC clearance to increase transplant viability.

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Section: Tolerance and Efferocytosis Or How Apoptotic Cells Direct Im...mentioning

confidence: 99%

Section: The Regulation Of Cd47 In Transplantationmentioning

confidence: 99%

The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles

Vafadar,

Vosough,

Jahromi

et al. 2023

Cell Biochemistry & Function

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“…In addition, miR-340 and miR-128 (pancreatic cancer), miR-222 (cervical cancer), miR-155 (MM), miR708 (breast cancer and acute lymphocytic leukemia), miR-7 (breast cancer), miR-133a (esophageal squamous cell carcinoma), miR-192 (medulloblastoma), and miR-423-5p (uveal melanoma) can inhibit the expression of CD47 and tumor growth. This field has been reviewed in detail by Savardashtaki and co-workers . The expression level of SIRPα was also influenced by the expression of miRs.…”

Section: Therapy Strategies Targeted On the Cd47-sirpα Axismentioning

confidence: 99%

“…This field has been reviewed in detail by Savardashtaki and co-workers. 91 The expression level of SIRPα was also influenced by the expression of miRs. Researchers have shown that SIRPα is the target gene of miR-17, miR-20a, and miR-106a, and lipopolysaccharide activation of macrophages will upregulate the expression of the above miRs, while the expression of SIRPα is inhibited.…”

Section: Antibody and Fusion Proteinmentioning

confidence: 99%

Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis

et al. 2022

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Cancer is still a major disease that is currently difficult for humans to overcome. When the expression of the cluster of differentiation 47 (CD47) is upregulated, tumor cells interact with the macrophage inhibitory receptor signal regulatory protein α (SIRPα) to transmit the "Don't eat me" signal, thereby avoiding phagocytosis by the macrophages. Therefore, when the CD47-SIRPα axis is inhibited, the macrophages' phagocytic function can be restored and can also exert antitumor effects. This Review mainly introduces recent advances in tumor therapy targeted on the CD47-SIRPα axis, including the antibody and fusion protein, small molecule, gene therapy, cell therapy, and drug delivery system, to inhibit the function of CD47 expressed on tumor cells and promote tumor phagocytosis by macrophages. In addition, this Review also summarizes the current approaches to avoid anemia, a common side effect of CD47-SIRPα inhibitions, and provides ideas for clinical transformation.

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“…Viable cells express CD47 (“Do not Eat‐Me” signal) which binds to the signal regulatory protein α (SIRP‐α) on macrophages to prevent phagocytosis. 80,81 Early ACs downregulate CD47 and upregulate calreticulin. Adiponectin recognizes calreticulin on the cell surface of macrophages and promotes low‐density lipoprotein (LDL)‐related protein (LRP)‐dependent efferocytosis.…”

Section: Main Steps In Efferocytosismentioning

confidence: 99%

The regulation of efferocytosis signaling pathways and adipose tissue homeostasis in physiological conditions and obesity: Current understanding and treatment options

et al. 2022

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Obesity is associated with changes in the resolution of acute inflammation that contribute to the clinical complications. The exact mechanisms underlying unresolved inflammation in obesity are not fully understood. Adipocyte death leads to pro-inflammatory adipose tissue macrophages, stimulating additional adipocyte apoptosis. Thus, a complex and tightly regulated process to inhibit inflammation and maintain homeostasis after adipocyte apoptosis is needed to maintain health. In normal condition, a specialized phagocytic process (efferocytosis) performs this function, clearing necrotic and apoptotic cells (ACs) and controlling inflammation. For efficient and continued efferocytosis, phagocytes must internalize multiple ACs in physiological conditions and handle the excess metabolic burden in adipose tissue. In obesity, this control is lost and can be an important hallmark of the disease. In this regard, the deficiency of efferocytosis leads to delayed resolution of acute inflammation and can result in ongoing inflammation, immune system dysfunction, and insulin resistance in obesity. Hence, efficient clearance of ACs by M2 macrophages could limit long-term inflammation and ensue clinical complications, such as cardiovascular disease and diabetes. This review elaborates upon the molecular mechanisms to identify efferocytosis regulators in obesity, and the mechanisms that can improve efferocytosis and reduce obesity-related complications, such as the use of pharmacological agents and regular exercise.

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The regulation of CD47-SIRPα signaling axis by microRNAs in combination with conventional cytotoxic drugs together with the help of nano-delivery: a choice for therapy?

Cited by 12 publications

References 87 publications

The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles

The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles

Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis

The regulation of efferocytosis signaling pathways and adipose tissue homeostasis in physiological conditions and obesity: Current understanding and treatment options

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