Role of Cytokine-Inducible SH2 Domain-Containing (CISH) Protein in the Regulation of Erythropoiesis

Saeed Maymand; Asha L Lakkavaram; Wasan Naser; Parisa Rasighaemi; Daniel Dlugolenski; Clifford Liongue; John Stambas; Tania F de Koning-Ward; Alister C Ward

doi:10.3390/biom13101510

Role of Cytokine-Inducible SH2 Domain-Containing (CISH) Protein in the Regulation of Erythropoiesis

Biomolecules. 2023 Oct 12;13(10):1510. doi: 10.3390/biom13101510.

Authors

Saeed Maymand¹, Asha L Lakkavaram¹, Wasan Naser^{1

2}, Parisa Rasighaemi¹, Daniel Dlugolenski¹, Clifford Liongue^{1

3}, John Stambas^{1

3}, Tania F de Koning-Ward^{1

3}, Alister C Ward^{1

3}

Affiliations

¹ School of Medicine, Deakin University, Waurn Ponds, Geelong, VIC 3216, Australia.
² College of Science, University of Baghdad, Baghdad 10071, Iraq.
³ Institute for Mental and Physical Health and Clinical Translation, Deakin University, Waurn Ponds, Geelong, VIC 3216, Australia.

Abstract

The cytokine-inducible SH2 domain-containing (CISH) protein was the first member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators discovered, being identified in vitro as an inducible inhibitor of erythropoietin (EPO) signaling. However, understanding of the physiological role played by CISH in erythropoiesis has remained limited. To directly assess the function of CISH in this context, mice deficient in CISH were characterized with respect to developmental, steady-state, and EPO-induced erythropoiesis. CISH was strongly expressed in the fetal liver, but CISH knockout (KO) mice showed only minor disruption of primitive erythropoiesis. However, adults exhibited mild macrocytic anemia coincident with subtle perturbation particularly of bone marrow erythropoiesis, with EPO-induced erythropoiesis blunted in the bone marrow of KO mice but enhanced in the spleen. Cish was expressed basally in the bone marrow with induction following EPO stimulation in bone marrow and spleen. Overall, this study indicates that CISH participates in the control of both basal and EPO-induced erythropoiesis in vivo.

Keywords: CISH; EPO; SOCS; cytokine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anemia / genetics
Animals
Cytokines
Erythropoiesis* / physiology
Mice
Signal Transduction / physiology
Suppressor of Cytokine Signaling Proteins* / metabolism
src Homology Domains

Substances

Cytokines
cytokine inducible SH2-containing protein
Suppressor of Cytokine Signaling Proteins

Grants and funding

S.M. and A.L.L. were supported by Ph.D. stipends from Deakin University and W.N. by a stipend from the Iraq Higher Committee for Education Development (HCED).