A novel renal perivascular mesenchymal cell subset gives rise to fibroblasts distinct from classic myofibroblasts

• DOI: 10.1038/s41598-022-09331-5
• Publication Date: 2022-03-30T16:39:06Z
• Authors: Shun Minatoguchi; Shoji Saito; Kazuhiro Furuhashi; Yuriko Sawa; Masaki Okazaki; Yuko Shimamura; Ahmad Baseer Kaihan; Yusaku Hashimoto; Yoshinari Yasuda; Akitoshi Hara; Yasuyuki Mizutani; Ryota Ando; Noritoshi Kato; Takuji Ishimoto; Naotake Tsuboi; Nobutoshi Esaki; Makoto Matsuyama; Yukihiro Shiraki; Hiroki Kobayashi; Naoya Asai; Atsushi Enomoto; Shoichi Maruyama
• Keywords: Myofibroblast

Perivascular mesenchymal cells (PMCs), which include pericytes, give rise to myofibroblasts that contribute chronic kidney disease progression. Several PMC markers have been identified; however, heterogeneity and functions are not fully understood. Here, we describe a novel subset of renal PMCs express Meflin, glycosylphosphatidylinositol-anchored protein was recently identified as marker fibroblasts essential for cardiac tissue repair. Tracing the lineage Meflin+ PMCs, found in perivascular periglomerular areas exhibit renin-producing potential, showed they detach from vasculature proliferate under conditions. Although contribution conventional α-SMA+ is low, with heterogeneous α-SMA expression patterns. Genetic ablation fibrosis mouse model revealed their role collagen production. Consistent this, human biopsy samples progressive diseases high Meflin expression. Furthermore, overexpression promoted bone morphogenetic 7 signals suppressed myofibroblastic differentiation, implicating roles suppressing fibrosis. These findings demonstrate marks functionally distinct classic pericytes myofibroblasts, highlighting importance elucidating heterogeneity.