JAK inhibitors could activate stem cells and help muscle repair

As we grow older, stem cells gradually lose their ability to repair and replace muscle. Two papers published in the journal Nature Medicine[1,2] give an explanation. Researchers found that the activation of JAK/STAT signaling pathway causes the reduced function of stem cells.

Gene expression analysis showed higher expression of JAK/STAT signaling proteins in satellite cells (muscle stem cells) from older adult relative to young mice. Activation of JAK/STAT signaling in satellite cells profoundly inhibits their capacity to undergo symmetric stem cell expansion.

Inhibition of JAK/STAT signaling by siRNA or small molecule inhibitors promotes the symmetric expansion of satellite cells in vitro. After intramuscular injection of JAK/STAT pathway inhibitors (AG490[3] and 5,15-DPP[4]), the satellite cells in older adult mice behaved the same as those found in young mice.

This approach of putting old stem cells back to work is similar to stem cell treatments. While this discovery is still at early stages, it gives the possibilities of JAK inhibitors for the treatment of muscle-wasting diseases. One concern is that over activation of stem cells may raise the risk of cancer.

JAK/STAT is a magic signaling pathway involving in various diseases. JAK inhibitors (ruxolitinib and tofacitinib) have been approved for the treatment of myelofibrosis and rheumatoid arthritis. Not long ago, it was reported that ruxolitinib offers hope for patients with alopecia areata (斑秃)[5].

[1] Nat Med. 2014, 20(10), 1182-1186.

[2] Nat Med. 2014, 20(10), 1174-1181.

[3] Leukemia. 2001, 15(5), 787-793.

[4] Biochem Biophys Res Commun. 2009, 380(3), 627-631.

[5] Nat Med. 2014, 20(9), 1043-1049.

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