What
is CLCF1 and how does it matter to the podocyte?
CLCF-1(
Cardiotrophin like cytokine factor-1) is a member of the interleukin 6 (IL-6) family of
cytokines, is also known as novel neurotrophin 1 and B cell–stimulating
factor-3.
CLCF1 is believed to be secreted
and present in circulation as a heterodimeric composite cytokine with either of
2 proteins, namely cytokine receptor-like factor (CRLF1) or soluble ciliary neurotrophic
factor receptor alpha (sCNTFRa).
The
role of CLCF1 in the regulation of podocyte structure and function is not
known. Studies have shown it’s interaction though with the activation of the Janus kinase-signal transducer and
activator of transcription (JAK-STAT) signaling pathway.
The investigators in a
recent study published detected CLCF1 in the plasma from patients with
recurrent FSGS. They studied the effect
of CLCF1 on isolated rat glomeruli using an in vitro assay of albumin permeability
(Palb). The CLCF-1 did cause maximal
increase in Palb. It was similar to an effect of having a FSGS serum. If they blocked the CLCF-1, the increase in
Palb was attenuated. The available JAK2
inhibitor blocked the effect of CLCF-1 or FSGS serum on Palb. STAT3 inhibitors also blocked this effect.
What do these findings mean?
1.
Could this be the permeability factor
that we are searching for fSGS?
2.
More needs to be understood regarding
this factor before making any strong conclusions
3.
Interestingly, could STAT3 or JAK2 inhibitors
could be potentially used to treat FSGS?
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