Thrombomodulin Expression by Human Keratinocytes. Induction of Cofactor Activity During Epidermal Differentiation

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1994 Apr 1

PMID 8163684

Citations 23

Authors

T J Raife

D J Lager

K C Madison

W W Piette

E J Howard

M T Sturm

Y Chen

S R Lentz

Affiliations

Soon will be listed here.

Abstract

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.

Citing Articles

Thrombomodulin: a multifunctional receptor modulating the endothelial quiescence.

Giri H, Biswas I, Rezaie A J Thromb Haemost. 2024; 22(4):905-914.

PMID: 38266676 PMC: 10960680. DOI: 10.1016/j.jtha.2024.01.006.

Human skin CD141 dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2.

Lui P, Ainali C, Chu C, Terranova-Barberio M, Karagiannis P, Tewari A iScience. 2023; 26(10):108029.

PMID: 37860766 PMC: 10583083. DOI: 10.1016/j.isci.2023.108029.

Chondrocyte Thrombomodulin Protects against Osteoarthritis.

Kang L, Yang A, Lai C, Chen T, Lin S, Wang Y Int J Mol Sci. 2023; 24(11).

PMID: 37298473 PMC: 10253941. DOI: 10.3390/ijms24119522.

Endotheliopathy is associated with slower liberation from mechanical ventilation: a cohort study.

Schonemann-Lund M, Itenov T, Larsson J, Lindegaard B, Johansson P, Bestle M Crit Care. 2022; 26(1):33.

PMID: 35094711 PMC: 8801241. DOI: 10.1186/s13054-021-03877-y.

Prognostic Significance of Thrombomodulin mRNA in High-Grade Soft Tissue Sarcomas after 10 years.

Asanuma K, Nakamura T, Asanuma Y, Okamoto T, Kakimoto T, Yada Y Orthop Surg. 2020; 12(6):1726-1732.

PMID: 33015987 PMC: 7767767. DOI: 10.1111/os.12779.

References

Griffin J, Evatt B, ZIMMERMAN T, Kleiss A, Wideman C . Deficiency of protein C in congenital thrombotic disease. J Clin Invest. 1981; 68(5):1370-3. PMC: 370934. DOI: 10.1172/jci110385. View

Stiernberg J, Redin W, Warner W, Carney D . The role of thrombin and thrombin receptor activating peptide (TRAP-508) in initiation of tissue repair. Thromb Haemost. 1993; 70(1):158-62. View

Gunning P, Ponte P, Okayama H, Engel J, Blau H, Kedes L . Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983; 3(5):787-95. PMC: 368601. DOI: 10.1128/mcb.3.5.787-795.1983. View

Esmon N, Carroll R, Esmon C . Thrombomodulin blocks the ability of thrombin to activate platelets. J Biol Chem. 1983; 258(20):12238-42. View

Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin A . Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med. 1984; 310(9):559-62. DOI: 10.1056/NEJM198403013100904. View

Maruyama I, Bell C, MAJERUS P . Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol. 1985; 101(2):363-71. PMC: 2113687. DOI: 10.1083/jcb.101.2.363. View

Maruyama I, MAJERUS P . The turnover of thrombin-thrombomodulin complex in cultured human umbilical vein endothelial cells and A549 lung cancer cells. Endocytosis and degradation of thrombin. J Biol Chem. 1985; 260(29):15432-8. View

Debault L, Esmon N, Olson J, Esmon C . Distribution of the thrombomodulin antigen in the rabbit vasculature. Lab Invest. 1986; 54(2):172-8. View

Morioka S, Lazarus G, Baird J, Jensen P . Migrating keratinocytes express urokinase-type plasminogen activator. J Invest Dermatol. 1987; 88(4):418-23. DOI: 10.1111/1523-1747.ep12469754. View

10.

Imada M, Imada S, Iwasaki H, Kume A, Yamaguchi H, Moore E . Fetomodulin: marker surface protein of fetal development which is modulatable by cyclic AMP. Dev Biol. 1987; 122(2):483-91. DOI: 10.1016/0012-1606(87)90312-5. View

11.

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

12.

Knedler A, HAM R . Optimized medium for clonal growth of human microvascular endothelial cells with minimal serum. In Vitro Cell Dev Biol. 1987; 23(7):481-91. DOI: 10.1007/BF02628418. View

13.

Boffa M, Burke B, Haudenschild C . Preservation of thrombomodulin antigen on vascular and extravascular surfaces. J Histochem Cytochem. 1987; 35(11):1267-76. DOI: 10.1177/35.11.2821107. View

14.

Yonezawa S, Maruyama I, Sakae K, Igata A, MAJERUS P, Sato E . Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin. Am J Clin Pathol. 1987; 88(4):405-11. DOI: 10.1093/ajcp/88.4.405. View

15.

Pillai S, Bikle D, Hincenbergs M, Elias P . Biochemical and morphological characterization of growth and differentiation of normal human neonatal keratinocytes in a serum-free medium. J Cell Physiol. 1988; 134(2):229-37. DOI: 10.1002/jcp.1041340208. View

16.

Esmon C . The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem. 1989; 264(9):4743-6. View

17.

Suzuki K, Nishioka J, Hayashi T, Kosaka Y . Functionally active thrombomodulin is present in human platelets. J Biochem. 1988; 104(4):628-32. DOI: 10.1093/oxfordjournals.jbchem.a122523. View

18.

Talwar H, Fisher G, Harris V, Voorhees J . Agonist-induced hydrolysis of phosphoinositides and formation of 1,2-diacylglycerol in adult human keratinocytes. J Invest Dermatol. 1989; 93(2):241-5. DOI: 10.1111/1523-1747.ep12277581. View

19.

Eckert R . Structure, function, and differentiation of the keratinocyte. Physiol Rev. 1989; 69(4):1316-46. DOI: 10.1152/physrev.1989.69.4.1316. View

20.

Dittman W, MAJERUS P . Structure and function of thrombomodulin: a natural anticoagulant. Blood. 1990; 75(2):329-36. View