A mutant fibrinogen that is unable to form fibrin can improve renal phenotype in mice with sickle cell anemia

Marilou G Narciso; Blair Hoeting; Jeanne M James; Katherine VandenHeuvel; Md Nasimuzzaman

doi:10.1002/jha2.204

A mutant fibrinogen that is unable to form fibrin can improve renal phenotype in mice with sickle cell anemia

EJHaem. 2021 Jun 15;2(3):462-465. doi: 10.1002/jha2.204. eCollection 2021 Aug.

Authors

Marilou G Narciso¹, Blair Hoeting¹, Jeanne M James², Katherine VandenHeuvel^{3

4}, Md Nasimuzzaman^{1

4}

Affiliations

¹ Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA.
² Division Pediatric Cardiology Medical College of Wisconsin Milwaukee Wisconsin USA.
³ Pathology Core Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA.
⁴ University of Cincinnati College of Medicine Cincinnati Ohio USA.

Abstract

Sickle cell anemia (SCA) causes nephropathy which may progress to kidney failure. To determine if soluble fibrinogen (Fib^AEK) can prevent kidney damage in mice with SCA, we performed bone marrow transplantation (BMT) of Berkeley sickle mice into wild-type fibrinogen (Fib^WT), and Fib^AEK mice that bear a germ-line mutation in fibrinogen Aα chain at thrombin cleavage site which prevents fibrin formation. We found improved albuminuria in SS Fib^AEK mice compared with SS Fib^WT mice at 12 months post-BMT due to the reduced kidney fibrosis, ischemic lesions, and increased survival of podocytes in the glomeruli, but did not improve urine concentrating defect. Therefore, our study clarifies the distinct role of fibrinogen and fibrin in the renal pathology of SCA.

Keywords: albuminuria; fibrinogen; kidney; nephropathy; pathology; sickle cell anemia; thrombin.