SMAD4 and hydrops fetalis: Once, TGF-β1 released it binds to receptor molecules (TGF-βRI & TGF-βRII) with subsequent phosphorylation events further engage in the TGF-β1/SMAD signaling cascade by creating a heterodimeric complex with the transcription factor SMAD4, culminating in the nucleus, causing gene transcription and fibroblast differentiation-induced cardiac fibrosis, and HF.38