Factor XIII-A transglutaminase acts as a switch between preadipocyte proliferation and differentiation

Myneni, Vamsee D.; Hitomi, Kiyotaka; Kaartinen, Mari T.

doi:10.1182/blood-2013-12-543223

Cited by 46 publications

(81 citation statements)

References 72 publications

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“…F13a1 gene expression is significantly upregulated in WAT of both obese patients and mice fed a HFD (49,50). Further, factor XIII has been suggested to act as a negative regulator of adipogenesis (50). Nevertheless, we show that loss of factor XIII activity does not phenocopy results observed in Fibγ 390-396A mice, as F13a1 -/-mice gain the same amount of weight as WT mice following HFD feeding.…”

Section: Discussionmentioning

confidence: 53%

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Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Kopec

Abrahams

Thornton

et al. 2017

Journal of Clinical Investigation

104

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Kopec

Abrahams

Thornton

et al. 2017

Journal of Clinical Investigation

104

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“…17,18 The transglutaminase enzyme family currently contains eight genes encoding active enzymes: Factor XIII-A and TG1-7 of which TG2 and FXIII-A are found in monocyte-macrophage lineage cells and number of cells of mesenchymal origin osteoblasts as well as in bone tissue. 13,15,[19][20][21][22][23][24] FN, a ubiquitous ECM glycoprotein required for cell adhesion, proliferation, survival and differentiation of many cell types [25][26][27] including bmMSCs, and osteoblasts, 28,29 is a well-known substrate for TGs, particularly for FXIII-A. [30][31][32] Postnatally, FN exists in two main forms which arise from alternate splicing of one gene: as the soluble, circulating plasma FN (pFN) produced by hepatocytes in liver, and as cellular FN (cFN) synthesized by certain tissue-resident cells.…”

mentioning

confidence: 99%

Transglutaminases factor XIII-A and TG2 regulate resorption, adipogenesis and plasma fibronectin homeostasis in bone and bone marrow

et al. 2017

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Appropriate bone mass is maintained by bone-forming osteoblast and bone-resorbing osteoclasts. Mesenchymal stem cell (MSC) lineage cells control osteoclastogenesis via expression of RANKL and OPG (receptor activator of nuclear factor κB ligand and osteoprotegerin), which promote and inhibit bone resorption, respectively. Protein crosslinking enzymes transglutaminase 2 (TG2) and Factor XIII-A (FXIII-A) have been linked to activity of myeloid and MSC lineage cells; however, in vivo evidence has been lacking to support their function. In this study, we show in mice that TG2 and FXIII-A control monocyte-macrophage cell differentiation into osteoclasts as well as RANKL production in MSCs and in adipocytes. Long bones of mice lacking TG2 and FXIII-A transglutaminases, show compromised biomechanical properties and trabecular bone loss in axial and appendicular skeleton. This was caused by increased osteoclastogenesis, a cellular phenotype that persists in vitro. The increased potential of TG2 and FXIII-A deficient monocytes to form osteoclasts was reversed by chemical inhibition of TG activity, which revealed the presence of TG1 in osteoclasts and assigned different roles for the TGs as regulators of osteoclastogenesis. TG2- and FXIII-A-deficient mice had normal osteoblast activity, but increased bone marrow adipogenesis, MSCs lacking TG2 and FXIII-A showed high adipogenic potential and significantly increased RANKL expression as well as upregulated TG1 expression. Chemical inhibition of TG activity in the null cells further increased adipogenic potential and RANKL production. Altered differentiation of TG2 and FXIII-A null MSCs was associated with plasma fibronectin (FN) assembly defect in cultures and FN retention in serum and marrow in vivo instead of assembly into bone. Our findings provide new functions for TG2, FXIII-A and TG1 in bone cells and identify them as novel regulators of bone mass, plasma FN homeostasis, RANKL production and myeloid and MSC cell differentiation.

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“…Whereas, in early embryonic life, the cells positive for cFXIII-A are the mesenchymal histiocytes and hepatocytes [18], in adult life, in addition to monocytes and tissue macrophages [3], cFXIII-A was detected also in DCs [4], fibroblasts [5], sebocytes [7], and mast cells of the skin and recently in the subcutaneous preadipocytes [19]. Although it is outside the scope of this review, osteoblasts, chondrocytes [20, 21], and cornea cells [22] should also be listed here as FXIII-A-producing cells [23, 24].…”

Section: Intracellular Fxiii-amentioning

confidence: 99%

“…Modulation of cytoskeletal dynamics induced the proliferation of the cells and at the same time inhibited their differentiation into lipid-accumulating mature adipocytes. FXIII-A, via the same pathway, might also be crucial in the transformation of embryonic fibroblasts into adipocytes [19]. More and more evidence supports that subcutaneous adipose tissue is in direct communication with the dermis through altering local inflammation and defense mechanisms against pathogens [42].…”

Section: Intracellular Fxiii-amentioning

confidence: 99%

Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment

Paragh

Törőcsik

2017

BioMed Research International

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The role of factor XIII subunit A (FXIII-A) is not restricted to hemostasis. FXIII-A is also present intracellularly in several human cells and serves as a diagnostic marker in a wide range of dermatological diseases from inflammatory conditions to malignancies. In this review, we provide a guide on the still controversial interpretation of dermal cell types expressing FXIII-A and assess the previously described mechanisms behind their accumulation under physiological and pathological conditions of the human skin. We summarize the intracellular functions of FXIII-A as well as its possible sources in the extracellular space of the dermis with a focus on its relevance to skin homeostasis and disease pathogenesis. Finally, the potential role of FXIII-A in wound healing, as a field with long-term therapeutic implications, is also discussed.

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Factor XIII-A transglutaminase acts as a switch between preadipocyte proliferation and differentiation

Abstract: Key Points Preadipocytes produce factor XIII-A, which acts as a negative regulator of adipogenesis by increasing plasma fibronectin matrix assembly. Factor XIII-A and plasma fibronectin matrix promote preadipocyte proliferation and proproliferative effects of insulin.

Cited by 46 publications

References 72 publications

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Transglutaminases factor XIII-A and TG2 regulate resorption, adipogenesis and plasma fibronectin homeostasis in bone and bone marrow

Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment

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