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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