Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis

The mechanism of H. pylori-induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against H. pylori infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach. Increase of IL-1β release from apoptotic macrophages and enhancement of TH1-polarized immune responses caused STAT1 and NF-κB activation in epithelial cells in ASK1 knockout mice. Dysregulated immune and epithelial activation in ASK1 knockout mice led to dramatic expansion of gastric progenitor cells and massive metaplasia development. Bone marrow transplantation experiments revealed that ASK1 in inflammatory cells is critical for inducing immune disorder and metaplastic changes in epithelium, while ASK1 in epithelial cells regulates cell proliferation in stem/progenitor zone without changes in inflammation and differentiation. These results suggest that H. pylori-induced immune cells may regulate epithelial homeostasis and cell fate as an inflammatory niche via ASK1 signaling.

Download Full-text

Pathophysiology of pachyonychia congenita‐associated palmoplantar keratoderma: new insights into skin epithelial homeostasis and avenues for treatment

British Journal of Dermatology ◽

10.1111/bjd.18033 ◽

2019 ◽

Vol 182 (3) ◽

pp. 564-573 ◽

Cited By ~ 10

Author(s):

A.G. Zieman ◽

P.A. Coulombe

Keyword(s):

Palmoplantar Keratoderma ◽

Epithelial Homeostasis ◽

Pachyonychia Congenita

Download Full-text

Acute exposure to fipronil induces oxidative stress, apoptosis and impairs epithelial homeostasis in the midgut of the stingless bee Partamona helleri Friese (Hymenoptera: Apidae)

The Science of The Total Environment ◽

10.1016/j.scitotenv.2021.145679 ◽

2021 ◽

Vol 774 ◽

pp. 145679

Author(s):

Cliver Fernandes Farder-Gomes ◽

Kenner Morais Fernandes ◽

Rodrigo Cupertino Bernardes ◽

Daniel Silva Sena Bastos ◽

Gustavo Ferreira Martins ◽

...

Keyword(s):

Oxidative Stress ◽

Stingless Bee ◽

Acute Exposure ◽

Epithelial Homeostasis

Download Full-text

Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00378-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Mingsen Li ◽

Liqiong Zhu ◽

Jiafeng Liu ◽

Huaxing Huang ◽

Huizhen Guo ◽

...

Keyword(s):

Epithelial Cells ◽

Corneal Epithelium ◽

Corneal Ulcer ◽

Corneal Epithelial ◽

Ocular Development ◽

Rieger Syndrome ◽

Corneal Ulcers ◽

Epithelial Homeostasis ◽

Forkhead Box ◽

Interferon Regulatory Factor 1

AbstractForkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld–Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells, but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer.

Download Full-text

Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10–p63 axis in epithelial homeostasis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1710726114 ◽

2017 ◽

Vol 114 (46) ◽

pp. 12243-12248 ◽

Cited By ~ 27

Author(s):

Bum-Ho Bin ◽

Jinhyuk Bhin ◽

Mikiro Takaishi ◽

Koh-ei Toyoshima ◽

Saeko Kawamata ◽

...

Keyword(s):

Progenitor Cell ◽

Hair Follicles ◽

Zinc Transporter ◽

Outer Root Sheath ◽

Epithelial Homeostasis ◽

Cell Proliferation And Differentiation ◽

Root Sheath ◽

Signaling Axis ◽

Progenitor Cell Proliferation ◽

Epidermal Development

Skin tissues, in particular the epidermis, are severely affected by zinc deficiency. However, the zinc-mediated mechanisms that maintain the cells that form the epidermis have not been established. Here, we report that the zinc transporter ZIP10 is highly expressed in the outer root sheath of hair follicles and plays critical roles in epidermal development. We found that ZIP10 marked epidermal progenitor cell subsets and that ablating Zip10 caused significant epidermal hypoplasia accompanied by down-regulation of the transactivation of p63, a master regulator of epidermal progenitor cell proliferation and differentiation. Both ZIP10 and p63 are significantly increased during epidermal development, in which ZIP10-mediated zinc influx promotes p63 transactivation. Collectively, these results indicate that ZIP10 plays important roles in epidermal development via, at least in part, the ZIP10–zinc–p63 signaling axis, thereby highlighting the physiological significance of zinc regulation in the maintenance of skin epidermis.

Download Full-text