HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients

Yuji Iimuro1,4, Akito Yada1, Toshihiro Okada1, Ikuo Nakamura1, Kazuhiro Suzumura1, Jinyang Xu1, Makoto Sudo1, Shuhei Nishiguchi2, Norifumi Kawada3, Etsuro Hatano1 and Jiro Fujimoto1

1Department of Surgery, 2Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan, 3Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan and 4Department of Surgery, Yamanashi Central Hospital, Yamanashi, Japan

Offprint requests to: Yuji Iimuro MD, PhD, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. e-mail: siimuro@hyo-med.ac.jp


Summary. Background and Aim. Among several noninvasive evaluation methods of portal hypertension (PH), the measurement of spleen stiffness is a reliable method for predicting esophageal variceal bleeding; however, the underlying mechanisms for increased stiffness remain unclear. We attempted to elucidate the pathological changes to the spleen and the underlying mechanisms in patients with PH. Methods. Histological examination was performed using splenic tissues from 42 patients with PH who underwent laparoscopic splenectomy, and the results were compared with those from patients without PH. Results. In addition to splenic sinus congestion, diffuse fibrosis was detected in the splenic cords in the red pulp of patients with PH. The degree of the fibrosis was well correlated with severity in thrombocytopenia and splenomegaly. Cells expressing α-smooth muscle actin dramatically increased in the splenic cord. Cytoglobin (Cygb) expression was detected in human splenic cords as reported in animal reticular cells, and fluorescent double immunostaining revealed that these cells expressed α-smooth muscle actin in patients with PH, suggesting transformation of Cygb-expressing cells to myofibroblastic cells. Expression levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2, nitrotyrosine, and transforming growth factor-β were markedly upregulated in the red pulp of patients with PH, implying a significant role of oxidative stress in the mechanism for splenic fibrosis. Conclusion. Splenic fibrosis progresses along with advancement of PH. Cygb-expressing cells in the splenic cord possibly participate in this process through mechanisms including oxidative stress. Histol Histopathol 35, 1319-1328 (2020)

Key words: Cytoglobin, Oxidative stress, Portal hypertension, Splenomegaly, Splenic fibrosis

DOI: 10.14670/HH-18-257