Dermal melanocortin receptor rebound in diffuse systemic sclerosis after anti-TGFβ1 antibody therapy.
Disturbed transforming growth factor beta (TGFβ) signalling leads to enhanced synthesis of extracellular matrix (ECM), which is manifested as systemic sclerosis (SSc), but this may be attenuated by the melanocortin system. Here, we report of rebound reaction in the gene expression of melanocortin receptor (MCR) subtypes and of the precursor of these receptors' ligands, the pro-opio-melanocortin protein (POMC), in the acute skin lesion of diffuse systemic sclerosis (dSSc) after treatment with a recombinant human anti-TGFβ1 antibody. Biopsies, taken from the leading edge of the skin lesion, before and after treatment of a patient with recent onset dSSc, were examined. Before treatment, increased levels of TGFβ mRNA and suppressed levels of POMC mRNA and MCR subtypes MC(1-3, 5) R mRNAs were seen in the lesion, compared with healthy controls. After treatment, there was a rebound expression of POMC, MC(2, 3, 5) R mRNAs. As the melanocortin system regulates collagen and melanin production, our findings add a new understanding to the pathogenetic mechanisms involved in the acute skin lesion of dSSc, which is characterized by enhanced ECM formation and changes in skin pigmentation.
Clinic of Rheumatology, Hospital of Vendsyssel/Ålborg University, Hjørring, Denmark. grethe.andersen.2@rn.dk
G Neumann
GN
Andersen
M
M
Andersen
O
O
Nagaeva
J E S
JE
Wikberg
L
L
Mincheva-Nilsson
D000906:Antibodies / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D044101:Receptors, Melanocortin / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D045743:Scleroderma, Diffuse / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000906:Antibodies; D012333:RNA, Messenger; D044101:Receptors, Melanocortin; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D011333:Pro-Opiomelanocortin