Ciclosporin does not influence bone marrow-derived cell differentiation to myofibroblasts early after renal ischemia/reperfusion.
BACKGROUND
Ischemia/reperfusion injury (IRI) is a risk factor for the development of interstitial fibrosis. Previously we had shown that after renal IRI, bone marrow-derived cells (BMDC) can differentiate to interstitial myofibroblasts. Here we hypothesized that the immunosuppressant ciclosporin A (CsA), known for its profibrotic side effect, promotes myofibroblast differentiation of BMDC in the postischemic kidney.


METHODS
Using a model of unilateral renal IRI in rats reconstituted with R26-human placental alkaline phosphatase transgenic bone marrow, CsA was administered in a previously defined critical window for differentiation of BMDC to myofibroblasts. We evaluated fibrotic changes in the kidney and myofibroblast differentiation of BMDC on day 14 after CsA treatment.


RESULTS
CsA treatment for 14 days led to increased transforming growth factor-beta transcript levels and collagen III deposition in the postischemic kidney. However, neither the total number of alpha-smooth-muscle-actin-positive interstitial myofibroblasts, nor the bone marrow-derived fraction thereof was affected by CsA administration, irrespective of dosage and duration of treatment.


CONCLUSIONS
In the critical postischemic window of BMDC differentiation to myofibroblasts, CsA did not promote BMDC differentiation to myofibroblasts, suggesting that, in the clinical setting, CsA is not involved in myofibroblastic differentiation of BMDC.
Broekema
Martine
M
Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Harmsen
Martin C
MC
Koerts
Jasper A
JA
van Kooten
Theo G
TG
Uges
Donald R A
DR
Petersen
Arjen H
AH
van Luyn
Marja J A
MJ
Navis
Gerjan
G
Popa
Eliane R
ER
D000199:Actins / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007511:Ischemia; D007668:Kidney / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000188:drug therapy*; D013234:Stem Cells / Q000378:metabolism
D000199:Actins; D004791:Enzyme Inhibitors; D016572:Cyclosporine