Peptidoglycan-Mediated Bone Marrow Autonomic Neuropathy Impairs Hematopoietic Stem/Progenitor Cells via a NOD1-Dependent Pathway in db/db Mice

Figure 5

A NOD1-specific inhibitor ameliorated PGN-mediated neurodegeneration in the bone marrow of diabetic mice and ultimately restored HSPC numbers and functions. (a) The upper images show representative tyrosine hydroxylase IHC staining of the femurs of mice from each group. The bottom quantitative data show that ML130, a specific inhibitor of NOD1, restored the number of try-OH⁺ nerve fibers in the bone marrow of PGN-treated db/db mice ( per group). (b) The upper images show representative NF200 IHC staining of mouse femurs. The bottom quantitative data show that ML130 protected against the PGN-induced degeneration of NF200⁺ neurons in the bone marrow of db/db mice ( per group). (c) Representative images of HSPC subpopulations (LSK, LT-HSC, and ST-HSC) analyzed by flow cytometry. (d–f) ML-130 ameliorated the PGN-mediated depletion of bone marrow (e) LT-HSCs in diabetic mice. No changes in the percentages of the (d) LSK and (f) ST-HSC populations were observed among the groups ( per group). (g) CFU assay shows ML130 ameliorated the increase in the number of BM CFU-G/M/GM and the decrease in the number of total CFUs in the blood induced by PGN in diabetic mice ( per group). (h) LSK cells from each group were cultured and tested for colonies in the LTC-IC assay ( per group). (i) For the in vivo BrdU incorporation study, the percentages of LT-LSK cells in each group were analyzed by FACS ( per group). Data represent . PGN: peptidoglycan; V: vehicle; LSK: Lin^-/CD127^-/Sca-1⁺c-Kit⁺; LT-HSC: long-term repopulating hematopoietic stem cell; ST-HSC: short-term repopulating hematopoietic stem cell. , ; ^&compared to db/m+V; ^#compared to db/db+PGN; ^§compared to db/db+V.

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