Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.
Title | Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Rana I, Kataria S, Tan TLin, Hajam EYousaf, Kashyap DKumar, Saha D, Ajnabi J, Paul S, Jayappa S, Ananthan ASHP, Kumar P, Zaarour RF, Haarshaadri J, Kansagara G, Rizvi A, Zirmire RK, Badarinath K, Khedkar SUday, Chandra Y, Samuel R, George R, Danda D, Jacob PMazhuvanch, Dey R, Dhandapany PS, He Y-W, Varga J, Varghese S, Jamora C |
Journal | J Invest Dermatol |
Volume | 143 |
Issue | 5 |
Pagination | 699-710.e10 |
Date Published | 2023 May |
ISSN | 1523-1747 |
Keywords | Animals, Disease Models, Animal, Extracellular Matrix Proteins, Fibroblasts, Fibrosis, Humans, Mice, Mice, Transgenic, Neoplasm Proteins, Scleroderma, Systemic, Skin |
Abstract | Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor SNAI1 is overexpressed in the epidermis of patients with systemic sclerosis, and a transgenic mouse recapitulating this expression pattern is sufficient to induce many clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin (SPON2) in fibrogenesis. Mindin is produced by SNAI1 transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis. |
DOI | 10.1016/j.jid.2022.10.011 |
Alternate Journal | J Invest Dermatol |
PubMed ID | 36528128 |
Grant List | R01 AR053185 / AR / NIAMS NIH HHS / United States |