Skin fibrosis caused by excessive collagen synthesis and deposition in the dermis affects the quality of daily life of hundreds of thousands of people around the world. The skin quality, including its smoothness at a young age and wrinkly during the aging process, depends mostly on the levels of extracellular matrix proteins such as collagen in the skin. As collagen’s physiological levels are desirable for skin homeostasis, beauty, and flexibility, too much collagen deposition in the skin is associated with tight hard skin, loss of fatty layer, flexibility, and pathological manifestations of skin fibrosis in fibrotic diseases such as scleroderma. To understand the molecular basis of skin fibrosis and in search of its therapy, different cellular, molecular, epigenetic, and preclinical studies have been undertaken to control abnormal excessive synthesis and accumulation of matrix protein collagen.

Over the last two decades, numerous phase 1 through 3 clinical trials have been conducted to test the safety and efficacy of a wide variety of compounds in amelioration of skin fibrosis, and other pathologies in scleroderma no effective therapy for skin fibrosis is available. The underlying molecular basis of agonist‐activated PPAR‐γ‐mediated suppression of profibrogenic signaling and skin fibrogenesis is also highlighted.