Mesenchymal Stem Cells Recruit Macrophages to Alleviate Experimental Colitis Through TGFβ1

Abstract

Background/Aims: Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate dextran sulfate sodium (DSS) -induced colitis through modulation of transforming growth factor β (TGFβ) receptor signaling. However, the exact molecular mechanisms are not known. Methods: Here, we transplanted primary mouse MSCs or injected TGFβ1 into mice with DSS-induced colitis. Cells were purified by flow cytometry. Gene expression was analyzed by RT-qPCR. Results: We found that MSCs significantly alleviated the DSS-induced colitis, and the major sources for TGFβ1 were macrophages that were recruited by MSCs. Specific ablation of macrophages completely abolished the anti-inflammatory effects of MSCs. On the other hand, TGFβ1 administration, without the presence of MSCs, was sufficient to reduce the severity of DSS-induced colitis. Conclusions: Taken together, our data suggest that MSCs transplantation may recruit macrophages to produce TGFβ1, which mitigates the pathology of colitis. Thus, MSCs transplantation appears to be a promising therapy for severe enteritis.

Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

“…Transforming growth factor-beta ( TGF-β ), one of the members of the bone morphogenetic protein (BMP) superfamily, is highly expressed in the bone matrix and is closely associated with osteoblast differentiation and bone development [12]. It has been reported that macrophages recruited by transplantation of MSCs could produce TGFβ1 to mitigate the pathology of colitis [13]. The activation of ERK1/2 and small mothers against decapentaplegic homolog (Smad) signaling pathways leads to increased TGF-β1 -induced Cx43 expression, which is required for the differentiation of trophoblast cells [14].…”

TIPE2 Alleviates Systemic Lupus Erythematosus Through Regulating Macrophage Polarization

“…The M1 macrophages express nitric oxide synthase (iNOS) and some pro-inflammatory cytokines and toxin like reactive oxygen species (ROS) [34][35][36][37]. M2 macrophages are specified as expression of arginase, and surface markers CD163, CD206 and CD301 that are not expressed by M1 macrophages [11,23,24,26,[34][35][36][37][38][39][40]. Macrophage polarization has been shown to regulate a variety of biological processes, as recently nicely reviewed [41][42][43].…”

Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar Disc Degeneration

“…HNPSV cells were transfected with a plasmid carrying both a constitutively nuclear form for FoxO1 and a GFP reporter that were connected with a 2A sequence, as has been previously described [19][20][21]. The small 2A peptide sequences, when cloned between genes, allow for efficient, stoichiometric production of discrete protein products within a single vector through a novel "cleavage" event within the 2A peptide sequence [22][23][24][25]. The transfected cells were termed as HNPSV-nFoxO1.…”